CN107109488A

CN107109488A - The method predicted the method for the reaction to breast cancer treatment agent and treat breast cancer

Info

Publication number: CN107109488A
Application number: CN201580068041.7A
Authority: CN
Inventors: A·C·彼得森; H·乌帕尔
Original assignee: Mai Diweixun Prostate Treatment Ltd Co
Current assignee: Mai Diweixun Prostate Treatment Ltd Co; Medivation Prostate Therapeutics LLC
Priority date: 2014-12-12
Filing date: 2015-12-08
Publication date: 2017-08-29
Also published as: EP3230471B1; IL252587A0; US11186876B2; RU2017120330A; US20220056541A1; US11952634B2; RU2017120330A3; BR112017012142A2; KR20170095306A; JP2018504892A; WO2016094408A1; EP3230471A1; US10196693B2; AU2015360767A1; US20190169697A1; MX2017007707A; JP6735277B2; ES2748005T3; US20160168646A1; SG11201704425TA

Abstract

There is provided the method for the method that triple negative breast cancer is treated using androgen receptor inhibitor, and the possibility for the validity of screening this treatment.

Description

The method predicted the method for the reaction to breast cancer treatment agent and treat breast cancer

The cross reference of related application

This application claims the rights and interests of following U.S. Provisional Application, the entire disclosure is incorporated herein by reference：2014 No. 62/091,195 submitted on December 12, in；No. 62/142,504 submitted on April 3rd, 2015；With May 27 in 2015 No. 62/167,110 submitted day.

Sequence table

The application includes the sequence submitted and be incorporated herein by reference in their entirety with ASCII fromat by EFS-Web List.The ASCII is copied to be created in 12/04/2015, is named as 212181_0001_00_WO_SeqListing_ST25, greatly Small is 262,467 bytes.

Invention field

This area is related to breast cancer treatment.

Background of invention

Breast cancer is considered as the disease of genetic heterogeneity and bio-diversity.Have shown that the clinic approved for a long time It is related to the difference of gene expression to phenotypic difference.Tumor of breast research in the past has identified related from different clinical effectivenesses Breast cancer five kinds of different subtypes：Tube chamber A (ERs (ER)+))；Tube chamber B (ER+)；HER2 is overexpressed；Normal breast Sample；With substrate sample.Referring to Perou et al. .Nature, 406 (6797):747-52(2000)；Sorlie et al. .PNAS, 98 (19):10869-74(2001)。

Breast cancer biopsy and the analysis of specimens from pri generally include core and cell surface receptor (ER, PgR and HER2 assessment), HER2 gene magnification (if by the HER2 of immunohistochemistry (IHC) analysis not being to determine property), And other prognosis tests such as capilary invasion and attack and proliferation marker.For the targeting ER signal transduction pathway of ER+ diseases Endocrine therapy and HER2 targeted therapies for HER2+ diseases play a crucial role in the treatment of most of patient with breast cancers. However, lacking the effective of the patient of these acceptors (i.e. so-called " three is negative " breast cancer or " TNBC ") for its disease in identification Almost it is not in progress in terms of targeted therapy, and nonselective cytotoxic chemotherapy is still main therapeutic choice.

Androgen receptor (AR) is the nuclear hormone receptor of most common expression in breast cancer, although its originate or drive it is pernicious Function in tumour is unclear.In the research of 3093 breast cancer, in 77% aggressive tumor of breast and all AR expression (more than 10% IHC nuclear stainings) (Collins et al., Mod Pathol 2011 is observed in molecular phenotype；24 (7):924-931).However, Androgen Receptor Level is not assessed routinely, because they not yet show prediction to making at present The reaction of therapy.

The part for using AR inhibitor as the therapeutic scheme for treating breast cancer is proposed.See, e.g., Garay and Park,Am.J.Cancer Res.2012；2(4):434-445.Generated recently in terms of TNBC treatments emerging Interest.Whole miss predictions of ERs, progesterone receptor and HER2 three's expression will not be to available endocrine (tamoxifen Sweet smell, aromatase inhibitor) and anti-HER2 (Herceptin) targeted therapy react.10 to 35% such TNBC tumours table Up to androgen receptor (Ogawa et al., Int J.Clin, Oncol.2008；13:431435).AR targeted therapies may be proved to be Include the valuable treatment of three negative cancers for most of breast cancer.

Suppress despite the presence of by androgen receptor signal transduction as treating the side that breast cancer particularly treats TNBC The interest of formula, but still need to predict whether individual patient has reaction before treatment.Prediction particular patient is particularly Whether the test of possibility reacted to the treatment that suppresses androgen receptor signal transduction will be plan patient to TNBC patient The valuable instrument for the treatment of.

Summary of the invention

It is used for the method for the treatment of triple negative breast cancer there is provided screening in one embodiment, the treatment includes Using androgen receptor inhibitor, methods described includes determining the biological sample obtained from subject, to determine to obtain from subject Whether the biological sample obtained is classified as substrate sample hypotype or another hypotype.If biological sample is classified as not be substrate sample Hypotype, then when sample is classified as substrate sample hypotype compared with, the breast cancer treatment comprising androgen receptor inhibitor is more likely It is effective.

Additionally provide the screening treatment three comprising androgen receptor inhibitor in the subject for needing this treatment negative The method of the possibility of the validity of breast cancer treatment.This method includes：

The biological sample obtained from subject is determined, to determine whether biological sample is classified as substrate sample hypotype or another Plant hypotype；With

If wherein biological sample is classified as not be substrate sample hypotype, substrate sample hypotype phase is classified as with sample Than the breast cancer treatment comprising androgen receptor inhibitor is it is more likely that effective.

Additionally provide the possibility that the classifying biological samples from subject are treated to validity for triple negative breast cancer patient Property finger calibration method, the treatment includes androgen receptor inhibitor, and methods described includes：

Wherein it is classified as not be that the biological sample of substrate sample hypotype shows to include the breast cancer of androgen receptor inhibitor Treatment is more likely effective when being classified as substrate sample hypotype than sample.

In some embodiments of screening and sorting technique (being referred to as " above method "), by detecting shown in table 1 The expression of intrinsic gene set carry out the measure biological sample to determine whether biological sample is classified as substrate sample hypotype Or another hypotype.

In some embodiments of the above method, the substrate barycenter grader score of sample is consolidating shown in table 1 There is the expression of gene set to determine.

In an embodiment of the above method, if substrate barycenter grader score is less than or equal to 0.9, it is determined that Compared with substrate barycenter grader score is more than 0.9, the breast cancer treatment comprising androgen receptor inhibitor is in treatment subject When be more likely effective.In another embodiment, if substrate barycenter grader score is less than or equal to 0.6, It is determined that the breast cancer treatment comprising androgen receptor inhibitor may be bigger than substrate barycenter grader score in treatment subject It is more effective when 0.6.In another embodiment, if substrate barycenter grader score is in the range of 0.2 to 0.8, Breast cancer treatment comprising androgen receptor inhibitor is more likely effective when treating subject.In another embodiment party In case, if substrate barycenter grader score is in the range of 0.4 to 0.7, the breast cancer comprising androgen receptor inhibitor Treatment is more likely effective when treating subject.

In some embodiments of the above method, the substrate barycenter grader score and tube chamber A barycenter graders of sample The expression of intrinsic gene set shown in score from table 1 is determined.This method also includes from substrate barycenter being classified according to following equation Device score and tube chamber A barycenter graders score calculate the substrate and tube chamber A grader scores of weighting：

The substrate of weighting and tube chamber A graders score=- 0.25 (substrate barycenter grader score)+0.27 (tube chamber A barycenter Grader score)

If the substrate and tube chamber A graders score of wherein weighting are more than -0.3, classify with the substrate and tube chamber A of weighting Device score is compared less than or equal to -0.3, and the breast cancer treatment comprising androgen receptor inhibitor is more likely in subject Effectively.In another embodiment, if the substrate and tube chamber A graders score of weighting are more than -0.2, with weighting Substrate is compared with tube chamber A graders score less than or equal to -0.2, the breast cancer treatment comprising androgen receptor inhibitor by It is more likely effective in examination person.In another embodiment, if the substrate and tube chamber A grader scores of weighting are big In -0.25, then compared with the substrate and tube chamber A graders score of weighting are less than or equal to -0.25, suppress comprising androgen receptor The breast cancer treatment of agent is more likely effective in subject.

In some embodiments, for determining that the substrate of weighting and the equation of tube chamber A grader scores have following shape Formula：

The substrate of weighting and tube chamber A graders score=- 0.2468275 (substrate barycenter grader score)+0.2667110 (tube chamber A barycenter graders score)

In some embodiments of the above method, breast cancer is characterised by depositing for androgen receptor positive tumor cell .

In some embodiments of the above method, biological sample is selected from cell, tissue and body fluid.In some embodiments In, body fluid is selected from blood, lymph, urine, saliva, emulsion and nipple aspirate from ductal lavage fluid.In some embodiment party In case, tissue is obtained from biopsy.

In any above method, being determined the androgen receptor state of the cell of sample, (i.e. AR is positive relative AR is negative) measure.

The method that triple negative breast cancer is treated in subject is additionally provided, the subject, which has, to be included being classified as It is not the breast cancer of the breast cancer cell of substrate sample hypotype, methods described includes applying subject to be suppressed comprising androgen receptor The breast cancer treatment of agent, so as to treat the triple negative breast cancer in subject.

In an embodiment for the treatment of method, the breast cancer cell of subject is characterised by shown in table 1 The substrate barycenter grader score for being less than or equal to 0.9 that expression of the intrinsic gene set in the cell is determined.In treatment side In another embodiment of method, the breast cancer cell of subject is characterised by that substrate barycenter grader score is less than or equal to 0.6.In another embodiment for the treatment of method, the breast cancer cell of subject is characterised by that substrate barycenter grader is obtained Divide in the range of 0.2 to 0.8.In another embodiment for the treatment of method, the feature of the breast cancer cell of subject exists In substrate barycenter grader score in the range of 0.4 to 0.7.

In another embodiment for the treatment of method, the breast cancer cell of subject be characterised by weighting substrate and Tube chamber A graders score is more than -0.3.In another embodiment for the treatment of method, the feature of the breast cancer cell of subject It is that the substrate and tube chamber A graders score that weight are more than -0.2.In another embodiment for the treatment of method, subject's Breast cancer cell is characterised by that the substrate and tube chamber A graders score of weighting are more than -0.25.

Additionally provide for treat the triple negative breast cancer in subject in need include androgen receptor inhibitor Triple negative breast cancer treatment, wherein the treatment method includes：(a) biological sample from subject is determined to determine biology Whether sample is classified as substrate sample hypotype or another hypotype；If biological sample is classified as not be that substrate sample is sub- (b) Type, then treat to the subject using the triple negative breast cancer.

Additionally provide the therapeutic agent for the treatment treated for triple negative breast cancer or for subject in need, wherein institute It is androgen receptor inhibitor to state therapeutic agent, and the treatment includes：(a) biological sample from subject is determined to determine whether Whether biological sample is classified as substrate sample hypotype or another hypotype；If biological sample is classified as not be substrate (b) Sample hypotype, then apply the therapeutic agent to the subject.

The androgen receptor inhibitor for treating the triple negative breast cancer in subject is additionally provided, wherein from tested The biological sample of person has been measured to determine whether sample is classified as substrate sample hypotype or another hypotype.

The method that triple negative breast cancer is treated in the subject for needing to treat is additionally provided, including：(a) biological sample is determined Product are to determine whether biological sample is classified as substrate sample hypotype or another hypotype；If the biological sample is divided (b) Class applies the breast cancer treatment comprising androgen receptor inhibitor, so as to treat tested to be not substrate sample hypotype to subject The breast cancer of person.

In above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of, determine Biological sample is by shown in detection table 1 to determine whether biological sample is classified as substrate sample hypotype or another hypotype The expression of intrinsic gene is carried out.

In above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of, determine Biological sample includes the substrate barycenter grader score of the expression determination sample of the intrinsic gene set shown in table 1, wherein such as Fruit substrate barycenter grader score is less than or equal to 0.9, then using breast cancer treatment.In one embodiment, if substrate Barycenter grader score is less than or equal to 0.6, then using breast cancer treatment.In one embodiment, if substrate barycenter point Class device score is in the range of 0.2 to 0.8, then using breast cancer treatment.In another embodiment, if substrate barycenter point Class device score is in the range of 0.4 to 0.7, then using breast cancer treatment.

In above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of, determine Biological sample includes the substrate barycenter grader score and pipe of the expression determination sample of the intrinsic gene set shown in table 1 Chamber A barycenter grader scores, and the substrate and tube chamber A grader scores of weighting are calculated, if wherein the substrate and tube chamber A of weighting Grader score is more than -0.3, then applies breast cancer treatment to subject.In one embodiment, if weighting substrate and Tube chamber A graders score is more than -0.2, then using breast cancer treatment.In another embodiment, if weighting substrate and Tube chamber A graders score is more than -0.25, then using breast cancer treatment.

It is tested in above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of The breast cancer of person is further characterized in that the presence of androgen receptor positive tumor cell.

In above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of, hero swashs Plain acceptor inhibitor is selected from：The miscellaneous Shandong amine of grace, Bicalutamide, Flutamide, Nilutamide, ARN509, ketoconazole, acetic acid Ah's bit Dragon, VN/124-1 (TOK-001), orteronel (TAK-700), Finasteride, galeterone, CPA, Andarine, with and combinations thereof.The list of androgen receptor inhibitor is exemplary, is not meant to be restricted.

In certain embodiments, androgen receptor inhibitor is the miscellaneous Shandong amine of grace.In such embodiment, grace Miscellaneous Shandong amine is oral daily once, and dosage is 160mg.In some embodiments, the miscellaneous Shandong amine of grace is as including the miscellaneous Shandong amine of 160mg grace Single capsule apply.In other embodiments, the miscellaneous Shandong amine of grace is applied in the form of four capsules, and each capsule includes 40mg The miscellaneous Shandong amine of grace.

In above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of, comprising The breast cancer treatment of androgen receptor inhibitor is not also other anticancers of androgen receptor inhibitor comprising one or more. The other anticancers for not being androgen receptor inhibitor can be selected from endoxan, fluorouracil, 5 FU 5 fluorouracil, first ammonia butterfly Purine, thiotepa, carboplatin, cis-platinum, taxane, taxol, the taxol that protein is combined, docetaxel, vinorelbine, tamoxifen Sweet smell, Raloxifene, Toremifene, fulvestrant, gemcitabine, Irinotecan, Ipsapirone, Temozolomide, TPT is long Spring new alkali, vinblastine, eribulin, mutamycin, capecitabine, capecitabine, Anastrozole, Exemestane, Letrozole, Leuprorelin, abarelix, Bath woods, Goserelin, megestrol acetate, Risedronate, Pamidronate, ibandronic acid Salt, Alendronate, ground promise monoclonal antibody, zoledronate, Herceptin, Lapatinib or Avastin, with and combinations thereof. The list of other anticancers is exemplary, is not meant to be restricted.

In one embodiment, non-AR inhibitor anticancer is taxol.In another embodiment, AR inhibitor It is the miscellaneous Shandong amine of grace, non-AR inhibitor anticancer is taxol.

In certain embodiments, treatment method includes test subject includes removing substrate to determine whether subject has The step of breast cancer of breast cancer cell outside sample hypotype.

In certain embodiments, treatment method includes test subject to determine the substrate of the breast cancer cell of subject The step of barycenter grader score.

In certain embodiments, treatment method includes test subject to determine the weighting of the breast cancer cell of subject Substrate and tube chamber A grader scores the step of.

It is tested in above-mentioned treatment method, treatment and some embodiments for the androgen receptor inhibitor for the treatment of The wheel prior treatment that person does not receive or received the anticancer in addition to androgen receptor inhibitor is negative to treat three Breast cancer.

In the reality of above-mentioned screening technique, sorting technique, treatment method, treatment and androgen receptor inhibitor for treatment Apply in scheme, biological sample can be selected from cell, tissue and body fluid.In certain embodiments, body fluid be selected from blood, lymph, Urine, saliva, ductal lavage fluid and nipple aspirate fluid.In some embodiments, tissue is obtained from biopsy.

In any of above screening technique, sorting technique, treatment method, treatment and androgen receptor inhibitor for treatment Embodiment in, the survey of the androgen receptor state (i.e. AR positive relative AR negative) of the cell of sample can be determined It is fixed.

As contemplated by the present invention on the composition and method of disclosed material, in one aspect, the present invention Embodiment include component disclosed herein and/or step.On the other hand, embodiment of the present invention is substantially by herein Disclosed component and/or step composition.On the other hand, embodiment of the present invention is by component disclosed herein and/or step Composition.

Definition

One or more than one of article " one " and " one kind " grammar object herein for being used to refer to the article are (i.e. extremely It is few one).As an example, " element " refers to an element or more than one element.

" about " will be understood by those of ordinary skill in the art, and by according to using its context and to a certain extent Change.As used herein, " about " it is intended to include ± 20% or ± 10%, more preferably ± 5%, even more preferably ± 1%, it is also more excellent The change of choosing ± 0.1%.

" androgen receptor inhibitor " refers to the chemical combination for directly or indirectly suppressing androgen receptor (AR) signal transduction pathway Thing or molecule.In one embodiment, the direct inhibitor of AR acceptors includes the miscellaneous Shandong amine of grace, Bicalutamide (Casodex), fluorine His amine, Nilutamide, ARN509 etc..In another embodiment, AR indirect inhibitor includes the inhibitor of Cyp 17, for example Ketoconazole, abiraterone acetate, VN/124-1 (TOK-001), orteronel (TAK-700) etc..In another embodiment In, AR inhibitor includes Finasteride, galeterone, CPA and andarine etc..

" detection expression " is intended to determine the RNA transcript of intrinsic gene or the quantity of its expression product or presence.

" suppression " or the suppression of other forms mean to hinder or suppress special characteristic.It should be understood that this generally with some standards Or desired value is related, in other words it is relative, but this is not always required for standard or relative value.

As it is used herein, " subject " means individual, typically mammal or poultry.Mammal can include Such as performing animal (such as cat or dog), domestic animal (such as ox, horse, pig, sheep, goat etc.), experimental animal (such as mouse, rabbit, Rat, cavy etc.) and primate.Preferably, mammal is people.

" triple negative breast cancer " or " TNBC " refers to not express ERs (ER), PgR (PR) and Her2/neu Gene any breast cancer.The term includes primary epithelial TNBC, and is related to the TNBC of other tumours.Cancer can be with Including triple negative breast cancer, breast ductal cancer, lobular carcinoma of breast, undifferentiated breast cancer, mammary gland capsule granuloma, mammary gland blood vessel Sarcoma and primary breast lymphoma.TNBC can also include any stage of triple negative breast cancer, and can include having The tumor of breast of histology and ultra microstructure heterogeneous (for example, cell mixing type).

" TNBC comprising androgen receptor inhibitor is treated " is to include treating using the TNBC of androgen receptor inhibitor. The treatment can include other anticancers or chemotherapeutant.

" needs " TNBC treatment subject be with TNBC or present TNBC one or more symptoms subject or Relative to the subject for the risk that whole colony has increased development TNBC.Preferably, the subject for " needing " TNBC to treat It is the subject tormented by TNBC.

As used herein, " therapeutically effective amount " or " treatment effective dose " refers to containing being at least enough to produce therapeutic effect Medicament, compound, material or the composition of compound.Effective dose be prevention, healing, improvement, prevent or part prevent disease or The amount of therapeutic agent needed for the symptom of illness.

" treatment " or " therapy " is not meant to complete healing.It means that the symptom of underlying diseases is reduced, and/or cause One or more reductions in the basal cell of symptom, physiology or biochemical reason or mechanism.It should be understood that it is as used herein, subtract Few state meant relative to disease, includes the molecular state of disease, and the not exclusively physiological status of disease.

Brief description of the drawings

Fig. 1 is that the prescreening or screening of the clinical test that the miscellaneous Shandong amine of grace is assessed in the patient that its TNBC also expresses AR are recruited The result figure of some patients raised." diagnosis-" represents there is substrate sample hypotype by what PAM50 gene breast cancer Subtypes were determined Patient." diagnosis+" represents the patient of Her2, LumA, LumB or normal hypotype.According to the standard provided in embodiment 1, it will suffer from Person is chosen as " reactor " or " not reactor " of the miscellaneous Shandong amine treatment of grace.

Fig. 2A and 2B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.2." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 3 A and 3B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.3." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 4 A and 4B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.4." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 5 A and 5B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.5." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 6 A and 6B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.6." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 7 A and 7B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.65." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 8 A and 8B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.7." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Fig. 9 A and 9B are that patient gene's expression grader score of wherein substrate sample hypotype is identical with patient's reaction correlation The figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.8." diagnosis+" represents it Sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value.According to the standard provided in embodiment 1, patient is chosen as " reactor " of the miscellaneous Shandong amine treatment of grace or " not reacted Person ".

Figure 10 A and 10B are that the patient gene of wherein substrate sample hypotype expresses the grader score phase related to patient's reaction With the figure of TNBC clinical test results.Using patient's substrate barycenter grader score that threshold cutoff value is 0.9." diagnosis+" is represented Its sample, which meets the prognosis characterizations specified, includes the patient for the threshold cutoff value specified." diagnosis-" represents that sample is unsatisfactory for specifying threshold The patient of cutoff value.According to the standard provided in embodiment 1, patient is chosen as to " reactor " or " not anti-of the miscellaneous Shandong amine treatment of grace The person of answering ".

Figure 11 is included in the table of various patient's subgroups for being treated in clinical test with the miscellaneous Shandong amine of grace to the reaction of the miscellaneous Shandong amine of grace Show.Reaction is represented with the clinical benefit rate (CBR24) of >=24 weeks.Subgroup includes treatment of purpose (ITT) patient；It is appreciable Patient；Breast tumor tissues patient (the IHC AR of AR dyeing >=10%>=10%)；By PAM50 Subtypes device by mammary gland Tumor tissues are categorized as the patient (non-substrate PAM50) of non-substrate sample hypotype；Staging is patient's (substrate of substrate sample hypotype PAM50)；Pass through application<0.6, >=0.6,<0.7, >=0.7,<0.75 and >=0.75 specified cutoff value is from patient's substrate barycenter Grader score is come the Patient Sample A that is analyzed." DX- " represents that sample is unsatisfactory for specifying the patient of threshold cutoff value." DX+ " table Sample product meet the patient for specifying threshold cutoff value.Combination standard IHC AR are also show in Figure 11>=10% and DX+<0.6 number According to.

Figure 12 is various patient's subgroups for being treated in clinical test with the miscellaneous Shandong amine of grace enters one to the reaction of the miscellaneous Shandong amine of grace Step is represented.Reaction is represented with the clinical benefit rate (CBR24) of >=24 weeks.Subgroup includes treatment of purpose (ITT) patient；It can comment The patient estimated；Breast tumor tissues patient (the IHC AR of AR dyeing >=10%>=10%)；Be used as first (First Line) or The patient of the miscellaneous Shandong amine treatment of grace is applied in two (the second lines) treatment.Subgroup further comprises by answering substrate barycenter grader score With<Patient Sample A's subgroup that 0.6 cutoff value is analyzed (" Novel DX+ "), and comprising being controlled from the first and second lines The subgroup of the sample for the treatment of, will<0.6 cutoff value is applied to substrate barycenter grader score.

Figure 13 is to show the middle position progression free survival phase (MPS) that patient is treated as the miscellaneous Shandong amine of grace of the function of time Kaplan-Meier schemes.The curve, which corresponds to, to be accredited as meeting<The new prognosis characterizations of 0.6 substrate barycenter grader score Patient's (" Novel DX Pos ") of condition is relative to the patient's (" Novel DX Neg ") for being unsatisfactory for this definition.

Figure 14 A-14D include the result of the patient's reaction in the clinical test for the miscellaneous Shandong amine of medicine grace for treating TNBC. Gene expression analysis is carried out to patient's Breast Tumor Samples using the PAM50 of table 1 intrinsic gene sets.To each sample evaluating and base The Spearman rank correlations of original pattern gene expression barycenter, and it is assigned as " substrate barycenter grader score ".To each sample The Spearman rank correlations estimated with tube chamber A gene expression barycenter are judged, and are assigned as " tube chamber A graders score ".Suffer from The substrate and tube chamber A grader scores of the weighting of person's sample are determined by following formula：

The substrate of weighting and tube chamber A graders score=- 0.2468275 (substrate barycenter grader score)+0.2667110 (tube chamber A barycenter graders score).

Use the substrate and tube chamber A grader score cutoff values of weighting>- 0.2 (Figure 14 A),>- 0.25 (Figure 14 B),>-0.3 (Figure 14 C) and>- 0.35 (Figure 14 D), to analyze the response data of grace miscellaneous Shandong amine reaction/not.Data are as shown in Figure 14 A-14D.Every In individual figure, " diagnosis+" represents that its sample meets the patient for the specified prognosis characterizations for including specifying threshold cutoff value." diagnosis-" is represented Sample is unsatisfactory for specifying the patient of threshold cutoff value.According to the standard provided in embodiment 1, patient is chosen as to treat the miscellaneous Shandong amine of grace " reactor " or " not reactor ".

Figure 15 is included in the table of various patient's subgroups for being treated in clinical test with the miscellaneous Shandong amine of grace to the reaction of the miscellaneous Shandong amine of grace Show.Reaction is represented with the clinical benefit rate (CBR24) of >=24 weeks.Subgroup includes treatment of purpose (ITT) patient；It is appreciable Patient；Breast tumor tissues are categorized as to the patient (non-substrate PAM50) of non-substrate sample hypotype by PAM50 Subtypes device； Staging is the patient (substrate PAM50) of substrate sample hypotype；Applied with passing through>- 0.2,>- 0.25,>- 0.3 and>- 0.35 Cutoff value is specified in the substrate and tube chamber A graders score of weighting to analyze the patient of breast tumor tissue samples.“PR-AR DX- " represents that sample is unsatisfactory for specifying the patient of threshold cutoff value." PR-AR DX+ " represent that sample meets the trouble for specifying threshold cutoff value Person.It also show and controlled in the previous of medicine for not receiving or receiving the non-androgen receptor inhibitor for being once used for TNBC treatments Treat (" and 0-1 prior treatment ") afterwards or receive for TNBC treatment non-androgen receptor inhibitor medicine twice Or more time prior treatment (" and>=2 prior treatments ") sample of patient that is followed by the research by the treatment of grace miscellaneous Shandong amine Response data (application>The substrate and tube chamber A grader scores cutoff value of -0.25 weighting).

Figure 16 is the Kaplan- for showing the progression free survival phase of the miscellaneous Shandong amine treatment patient of grace as the function of 56 time-of-weeks Meier schemes.The curve, which corresponds to, is accredited as the substrate and tube chamber A grader scores (" PR-AR that meet the weighting more than -0.2 DX+：>- 0.2 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.2：<=-0.2 ", bottom Curve) characteristic condition patient.

Figure 17 is the Kaplan- for showing the progression free survival phase of the miscellaneous Shandong amine treatment patient of grace as the function of 56 time-of-weeks Meier schemes.The curve, which corresponds to, is accredited as the substrate and tube chamber A grader scores (" PR-AR that meet the weighting more than -0.25 DX+：>- 0.25 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.25：<=-0.25 ", Bottom curve) characteristic condition patient.

Figure 18 is the Kaplan- for showing the progression free survival phase of the miscellaneous Shandong amine treatment patient of grace as the function of 56 time-of-weeks Meier schemes.The curve, which corresponds to, is accredited as the substrate and tube chamber A grader scores (" PR-AR that meet the weighting more than -0.3 DX+：>- 0.3 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.30：<=-0.3 ", bottom Portion's curve) characteristic condition patient.

Figure 19 is the Kaplan- for showing the progression free survival phase of the miscellaneous Shandong amine treatment patient of grace as the function of 56 time-of-weeks Meier schemes.The curve, which corresponds to, is accredited as the substrate and tube chamber A grader scores (" PR-AR that meet the weighting more than -0.35 DX+：>- 0.35 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.35：<=-0.35 ", Bottom curve) characteristic condition patient.

Figure 20, which is shown in not receive or receive, is once used for the medicine for the non-androgen receptor inhibitor that TNBC is treated Prior treatment grace miscellaneous Shandong amine treatment patient progression free survival phase Kaplan-Meier figures.The curve corresponds to identified To meet the substrate and tube chamber A graders score (" PR-AR DX+ of the weighting more than -0.25：>- 0.25 ", top curve) it is relative In grader score (" the PR-AR DX- less than or equal to -0.25：<=-0.25 ", bottom curve) characteristic condition patient.

Figure 21 A and 21B including the use of>The substrate and tube chamber A grader score cutoff values of -0.25 weighting be not as connecing By or non-male swashing of receiving once that (0-1 prior treatment) or two or more times (2+ prior treatment) are used for that TNBC to treat The new prognosis of the predictive factor of the reaction of AR inhibitor for treating in the patient of the prior treatment of the medicine of plain acceptor inhibitor The figure of the effect of feature.Figure 21 B 56 patients are accredited as meeting the substrate weighted more than -0.25 and tube chamber A graders are obtained The characteristic condition divided.The 62 research patients identified by the grader score less than or equal to -0.25 are reflected in Figure 21 A It is fixed.Each bar in figure represents a patient.The patient's bar for indicating triangle is active (" active ") under study for action.Indicate Patient's bar of asterisk represents to react (CR) or partial reaction (PR) completely.

Figure 22 A and 22B include showing that the middle position of the miscellaneous Shandong amine treatment patient of grace as the function of time gets nowhere life respectively Deposit the phase Kaplan-Meier figures of (Figure 22 A) (mPFS) and Overall survival (mOS).Curve correspond to be accredited as meet be more than- The substrate and tube chamber A graders score (" PR-AR DX+ ", top curve) of 0.25 weighting are relative to less than or equal to -0.25 Grader score (" PR-AR DX- ", bottom curve) characteristic condition patient.Figure 22 A：Trouble for meeting characteristic condition Person, mPFS=16.1 weeks；Patient for being unsatisfactory for characteristic condition, mPFS=8.1 weeks.Figure 22 B：For meeting characteristic condition Patient, mOS=NYR (not yet the reaching) at 84 weeks；Patient for being unsatisfactory for characteristic condition, mOS=32.1 weeks.

Figure 23, which is shown in not receive or receive, is once used for the medicine for the non-androgen receptor inhibitor that TNBC is treated Prior treatment grace miscellaneous Shandong amine treatment patient progression free survival phase Kaplan-Meier figures.The curve corresponds to identified To meet the substrate and tube chamber A graders score (" PR-AR DX+ of the weighting more than -0.25:>- 0.25 ", top curve) it is relative In grader score (" the PR-AR DX- less than or equal to -0.25:<=-0.25 ", bottom curve) characteristic condition patient. The continuity of the research of tables of data diagram 20,64 weeks into Figure 23 of 56 weekly intervals more than Figure 20.In fig 23, it is special for meeting The patient for levying condition, mPFS=40.4 weeks；Patient for being unsatisfactory for characteristic condition, mPFS=8.9 weeks." NYR " refers in figure " not yet reaching " in the statement for 95% confidential interval (CI) that the data representated by the patient of characteristic condition are met in 23.

Figure 24 A, 24B and 24C are shown when the miscellaneous Shandong amine (Enza) of grace, taxol (PTX) or its group with prescribed concentration respectively When closing processing, TNBC cell lines BT549, MDA-MB-436 and MDA-MB-453 viability.It is presented flat for each cell line Average (n=5).

Figure 25 A and 25B are shown in (i) and feed the miscellaneous Shandong amine (Enza) of (PO) grace with 3mg/kg/ days (n=10) mouths, (ii) with 6mg/kg QMWF (IP) (n=7) taxol (PTX), or after (iii) (i) and (ii) (n=10) combination, transplanting has TNBC thin The growth of the tumour induced in the NOD-SCID mouse of born of the same parents system MDA-MB-453 cell.Measured under the number of days shown in Figure 25 A Gross tumor volume.Data point in Figure 25 A represents every group of mean tumour volume, and error bars reflect the SEM of data.In Figure 25 B Tumor weight was determined at the 35th day.

Detailed description of the invention

The invention provides the method for the TNBC in subject of the treatment with TNBC, wherein the subject influenceed by TNBC Breast cancer cell be characterised by be derived from expression of some intrinsic gene sets more specifically described below in those cells Score.(may be effectively) whether be recommended to be used to apply conduct present invention also offers the TNBC assessed comprising AR inhibitor treatments The method of TNBC patient's treatment course.Therefore, the present invention provides assess including the use of androgen receptor in one embodiment The method of the triple negative breast cancer treatment of body inhibitor, methods described includes determining the biological sample obtained from subject, with true Whether the fixed biological sample obtained from subject is classified as substrate sample hypotype or another hypotype.If biological sample is classified Not to be substrate sample hypotype, then when classifying sample as substrate sample hypotype compared with, the mammary gland comprising androgen receptor inhibitor Cancer is treated it is more likely that effective.Therefore, the present invention provides treatment and suffered from and includes being classified in one embodiment For be not substrate sample hypotype breast cancer cell cancer subject in triple negative breast cancer method.This method include pair Subject applies the breast cancer treatment comprising androgen receptor inhibitor, so as to treat the triple negative breast cancer in subject.

Invention further provides by determining whether TNBC patient should receive to include the treatment of AR inhibitor for treating, It is then based on the method that the determination applies optimal AR inhibitor for treating to treat TNBC to patient.Although the research being mentioned above is Patient Sample A's (including tumor sample) of AR acceptor stained positives is carried out by immunohistochemistry (IHC), but the present invention Scope be not limited to AR (+) TNBC treatment and prognosis.

Tumor of breast research based on intrinsic genetic analysis has identified five kinds of different subtypes of breast cancer：Tube chamber A (LumA), tube chamber B (LumB), HER2 are enriched with (Her-2-E), substrate sample and normal (Perou et al. .Nature, 406 (6797): 747-52(2000)；Sorlie et al. .PNAS, 98 (19):10869-74(2001)).HER2 enrichment hypotypes herein can be with It is referred to as " HER2 ", it should be understood that the latter also means that HER2 is enriched with hypotype.Substrate sample hypotype is properly termed as " substrate " herein, should Work as understanding, the latter also means substrate sample hypotype.Therefore, by the way that cell or sample distributed into above-mentioned hypotype, breast cancer sample or Cell is by " classification ".Breast cancer sample or cell may be considered as negativity " classification ", i.e., it is determined that cell or sample are After LumA, LumB, HER2 or normal sample hypotype, cell or sample can be categorized as " non-substrate " or " in addition to substrate ".

We have surprisingly found that the presence of substrate sample hypotype shows the clinical nothing to AR inhibitor for treating in TNBC The possibility of reaction.We have found that the substrate barycenter grader score less than or equal to 0.9 represents to face AR inhibitor The possibility of bed reaction.We have been unexpectedly discovered that, based on the substrate sample and pipe carried out to the biological sample from TNBC patient The empirically determined weight score of chamber A Subtypes shows the possibility of the clinical response to AR inhibitor for treating.Therefore, one In individual embodiment, the biological sample from the patient with TNBC is measured to determine breast cancer hypotype.At another In embodiment, the biological sample from the patient with TNBC is measured to determine substrate barycenter grader score, or Both substrate barycenter grader score and tube chamber A grader scores.

For determine biological sample whether be classified as the hypotype in addition to substrate sample hypotype measure can include be used for Determine the determination method of the presence of substrate sample hypotype；Negative findings represents non-basal subtype.Can use can identify that substrate sample is sub- Any determination method of the presence of type.About 70-90% three negative cancers be shown as substrate sample breast cancer (Bertucci et al., Int.J.Cancer2008,123,236–240；Wang et al. .Eur.J.Clin.Invest.2008,38,438-446), three Negative phenotype has been used as the substitute of substrate sample hypotype.However, research shows, three feminine genders and substrate sample tumor of breast are not same Justice.See, for example, Choo and Nielsen, Cancers 2010,2,1040-1065.Therefore, it is necessary to which carefully choosing is used for Identify the measure of substrate sample hypotype.

Recently, have issued for dependent on have been found to be the feature of substrate sample hypotype following characteristics spectrum substrate sample The measure of hypotype：ER is negative, and HER2 is negative, and CK5/6 and/or the HER1 positives.Therefore one group four is had been proposed Kind of antibody (ER, HER1, HER2 and CK5/6) as the immunohistochemistry spy for being used to identify mammary gland substrate sample tumour Levy (Nielsen et al., Clinical Cancer Research 2014；10:5367-5374).

Substrate sample and tube chamber A Subtypes are carried out by determination of gene expression, and the expression of its by the use of intrinsic gene is used as breast The grader gene of gland cancer classification.Intrinsic gene (such as Perou et al. (2000) Nature 406:Described in 747-752) united It is to have between the biological sample repetition thing of same individual with low change and between the sample of Different Individual to count and learn selection There is the height change of expression.The present invention utilizes PAM50 Gene Expression Assays (Parker et al. .J Clin Oncol., 27 (8):1160-7 (2009) and U.S. Patent Application Publication No. 2011/0145176, are hereby incorporated herein by full). PAM50 determination of gene expression can be used for identification from the standard biological sample such as tumor tissues of formalin fixation FFPE The intrinsic hypotype (tube chamber A, tube chamber B, HER2 enrichment, substrate sample and normal sample) of breast cancer.PAM50 gene expressions classification device is prison The Forecasting Methodology based on barycenter superintended and directed, breast cancer classification is above-mentioned five kinds of molecules using the intrinsic gene expression characteristicses of 50 genes by it One of hypotype.

Such as Parker et al. and U.S. Patent Application Publication No. 2011/0145176 and U.S. Patent Application Publication No. Described in 2013/0004482, PAM50 determination of gene expression method utilizes and supervises algorithm according to the intrinsic hypotype of breast cancer to tested Person's sample is classified.The algorithm is referred to herein as " PAM50 disaggregated models " or " PAM50 graders ", and it is based on having identified The gene expression profile of 50 intrinsic genes for the intrinsic hypotype of breast cancer of classifying stator collection really.In U.S. Patent Application Publication Gene subset, and the specific primer for its detection are provided in number 2013/0004482 table 1, and is reproduced in below In the table 1 of present disclosure.The selection sequence of the intrinsic gene of identical 50 is as shown in table 2 below.Publication number 2013/0004482 Complete disclosure be incorporated herein by reference.

The detection and estimation of the expression of the set of 50 hypotype predicted genes of table 1 are carried out by any suitable means.

PAM50 gene expressions classify device by using the prototype hardware based on the objective selection for " training " algorithm spy The monitoring forecast algorithm for levying spectrum exploitation is operated.According to U.S. Patent Publication No. 2009/0299640, (entire contents pass through Be incorporated herein by reference) disclosed in method, use the intrinsic gene set selection of extension and sub- parting sample.According to hypotype to instruction After white silk sample is layered, using the prediction algorithm based on barycenter, the express spectra based on the intrinsic gene set shown in table 1 builds every The barycenter of individual molecular isoform.Barycenter is average gene expression divided by the gene of each gene in each hypotype (or " classification ") Classification internal standard deviation.Closest to barycenter classify obtain fresh sample gene expression profile, and by its with these class centroids Each is compared.By the way that the Spearman rank correlations of each test case are calculated to five barycenter of PAM50 hypotypes, and Sample is distributed to hypotype based on immediate barycenter, to complete hypotype prediction.

According to an embodiment, it is not necessarily referring to distribute Patient Sample A to PAM50 hypotypes, it is determined that with substrate sample base Because expressing the Spearman rank correlations of barycenter.Spearman rank correlations between sample and substrate sample barycenter are designated as " substrate barycenter grader score ".The Spearman rank correlations with tube chamber A gene expression barycenter are determined.Sample and tube chamber A Spearman rank correlations between barycenter are designated as " tube chamber A barycenter graders score ".Using the feature based on PAM50 with The method for providing substrate barycenter grader score and tube chamber A barycenter grader scores is well known by persons skilled in the art.Referring to Such as U.S. Patent Application Publication No. 2009/0299640；Parker et al., J Clin.Oncol., 27 (8):1160-7 (2009)；U.S. Patent Application Publication No. 2011/0145176.Referring also to such as Prat et al., British Journal Of Cancer, (2014) 111,1532-1541, it is incorporated herein by reference.

Clinical test such as the TNBC patient treated by using the miscellaneous Shandong amine of AR inhibitor grace is confirmed, it has been found that be less than Or the substrate barycenter grader score equal to 0.9 represents the possibility for having clinical response to AR inhibitor.In some embodiments In, predicted using the substrate barycenter grader score less than or equal to 0.9,0.2 to 0.8,0.4 to 0.7 to AR inhibitor The possibility of clinical response.In one embodiment, predicted using the substrate barycenter grader score less than or equal to 0.6 To the possibility of the clinical response of AR inhibitor.

We have further found that, substrate barycenter grader score and tube chamber A barycenter grader scores, when true with some experiences There is provided androgen receptor inhibitor is treated available for further prediction individual TNBC patient when fixed weight factor is combined Reactive score (" substrate and tube chamber A graders score of weighting ").The substrate and tube chamber A grader scores of weighting are under The equation in face is determined：

The substrate of weighting and tube chamber A graders score=- 0.25 (substrate barycenter grader score)+0.27 (tube chamber A barycenter Grader score).

Clinical test such as the TNBC patient treated with the miscellaneous Shandong amine of AR inhibitor grace is proved, if the substrate and pipe of weighting Chamber A graders score is more than -0.3, and patient is confirmed as the patient that may have reaction to AR inhibitor for treating.Or, if plus The substrate and tube chamber A graders score of power are more than -0.2, then can also be accredited as patient may have instead to AR inhibitor for treating The patient answered.Selection -0.25 can improve the degree of accuracy as prediction to the reactive cutoff value of AR inhibitor for treating.Therefore, In preferred embodiments, if the substrate and tube chamber A graders score of weighting are more than -0.25, patient is identified as possibility There is the patient of reaction to AR inhibitor for treating.If substrate and tube chamber A grader score quilts that TNBC patient passes through determination weighting The patient that there may be reaction to the AR inhibitor for treating for TNBC is identified as, then can apply appropriate AR inhibitor for treating and come Treat the TNBC illnesss of patient.

The substrate and tube chamber A graders score of weighting are used to predict patient to the effectiveness of the reaction of AR inhibitor for treating as schemed Shown in 14A-14D and Figure 15.Various TNBC patient's subgroups that accompanying drawing is included in clinical test with the miscellaneous Shandong amine treatment of grace are miscellaneous to grace The expression of the reaction of Shandong amine.The reactivity that patient treats to the miscellaneous Shandong amine of grace is related to the substrate and tube chamber A grader scores that weight, Using>- 0.2 (Figure 14 A),>- 0.25 (Figure 14 B),>- 0.3 (Figure 14 C) and>A series of -0.35 (Figure 14 D) cutoff values extremely add The substrate and tube chamber A grader scores of power.In " diagnosis-" and Figure 15 in Figure 14 A-D " PR-AR DX- " represent its sample not Meet substrate and the patient of tube chamber A grader score threshold cutoff values for the weighting specified.In " diagnosis+" and Figure 15 in 14A-D " PR-AR DX+ " represent that its sample meets the patient for specifying threshold cutoff value.From the consideration to data can be seen that more than- The substrate and tube chamber A graders score of 0.25 weighting provide prediction TNBC patient the miscellaneous Shandong amine of grace is treated it is reactive most High accuracy, using the standard more than -0.2 or more than -0.3, also provides acceptable result.

The Kaplan- of correlation between patient's reaction and the substrate and tube chamber A grader scores of weighting in Figure 16-19 Further illustrated in Meier figures, it is shown that use the nothing of the function as 56 time-of-weeks of the TNBC patient of the miscellaneous Shandong amine treatment of grace It is in progress life cycle.Curve in Figure 16 is obtained corresponding to the substrate and tube chamber A graders for being accredited as meeting the weighting more than -0.2 Divide (" PR-AR DX+：>- 0.2 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.2：< =-0.2 ", bottom curve) characteristic condition.Figure 17,18 and 19 are similar to Figure 16, wherein being applied more than -0.25 (Figure 17), greatly In -0.3 (Figure 18) and the characteristic condition more than -0.35 (Figure 19).It is appreciated that hanging down between each each upper curve of individually figure The amplitude directly separated is the precision of the correlation between the substrate and tube chamber A graders score and Progression free survival of patient's weighting Measure.On this basis, can be further understood from Figure 16-19 comparison year, using the weighting more than-0.25 substrate and The standard of tube chamber A graders score (Figure 17) is provided the substrate of weighting and tube chamber A graders score with TNBC patient to grace The associated most accuracy of miscellaneous Shandong amine therapeutic response, using more than -0.2 (Figure 16) or the standard more than -0.3 (Figure 18), There is provided acceptable result.

It has also been found that, it is used as the new weighting substrate and tube chamber of the reactive predictive factor of the AR inhibitor for treating to TNBC The acquisition in the patient treated no more than a previous TNBC of wheel is treated or received without the previous TNBC of receiving of A graders score The accuracy of even more high.From relatively can be seen that in 0 to 1 prior treatment patient's group for Figure 20 and 17, with all experiments Larger group of patient compares (Figure 17), and the substrate of the weighting more than -0.25 and the standard (Figure 20) of tube chamber A grader scores cause Identify the accuracy increase that the patient for having reaction is treated to the miscellaneous Shandong amine of grace, such as perpendicular separation relative to the curve in Figure 17, figure Larger perpendicular separation is proved between 20 curve.The trend, wherein Figure 20 research are further observed that in fig 23 64 weeks more than 56 weeks in Figure 20 into Figure 23 of Progression free survival time showing in object.

The result is also shown in Figure 21 A and 21B, it is shown that be accredited as meet more than -0.25 weighting substrate and 56 patients (Figure 21 B) of the characteristic condition of tube chamber A grader scores obtain with respect to the grader less than or equal to -0.25 Divide the degree (progression free survival phase) without progression of disease treatment time of 62 patients (Figure 21 A) of identification.Each bar is represented One patient.Patient is in the miscellaneous preceding elder generation in the medicine for not receiving or receiving once non-androgen receptor inhibitor of Shandong amine treatment of grace Prior treatment (the 2+ of the medicine of preceding TNBC treatments (0-1 prior treatment) or the non-androgen receptor inhibitor of two or more times Secondary prior treatment).The patient's bar for indicating triangle is active (" active ") under study for action.The patient's bar for indicating asterisk has been represented Full response (CR) or partial reaction (PR).Receive once or not to receive in the reactor of prior treatment without progression of disease Golden hour is obvious (Figure 21 B).

Correlation between patient's reaction and the substrate and tube chamber A grader scores of weighting is in Figure 22 A and 22B Further illustrated in Kaplan-Meier figures, the middle position progression free survival phase (mPFS) (Figure 22 A) and middle position of comparative studies patient The terminal of Overall survival (mOS) (Figure 22 B).Curve in Figure 22 A and 22B, which corresponds to, is accredited as meeting adding more than -0.25 The substrate and tube chamber A graders score (" PR-AR DX+ ", top curve) of power are relative to the grader less than or equal to -0.25 The patient of the characteristic condition of score (" PR-AR DX- ", bottom curve).Therefore, as a result show in addition to progression free survival phase, Substrate and tube chamber A graders more than the weighting of -0.25 score is also related to overall survival phase.It is unsatisfactory for prognosis characterizations condition Patient be characterized in 8.1 weeks middle position progression free survival phase and the middle position Overall survival of 32.1 weeks.By contrast, prognosis is met special The patient for levying condition is characterised by the middle position progression free survival phase of 16.1 weeks, and not yet reach middle position Overall survival within 84 weeks (mOS NYR)。

Gene expression detection

As determining the of the substrate barycenter grader score of TNBC patient or the substrate of weighting and tube chamber A grader scores One step, by any method the gene expression detection to the gene of the intrinsic gene set of Patient Sample A's carry out table 1 be used to determine The intrinsic RNA transcript of gene or the quantity of its expression product or presence.This method description is in U.S. Patent Application Publication No. In 2009/0299640 and 2013/0004482, it is incorporated herein by reference.They include for example based on polynucleotides hybridizing The method of analysis, the method being sequenced based on polynucleotides, immunohistochemical method and the method based on proteomics.It is described Method generally detects the expression product (such as mRNA) of intrinsic gene shown in table 1.

It can be used in one embodiment as the RNA sequencings of the method for determining gene expression.Intrinsic gene The gene expression detection of collection can also be included but is not limited to real by being carried out for assessing gene expression/quantitative other technologies When PCR, microarray, microfluid gene expression and target gene sequencing.These methods include the hybridization analysis of such as polynucleotides, The method being sequenced based on polynucleotides, immunohistochemical method and the method based on proteomics.PCR-based can be used Method, such as reverse transcription PCR (RT-PCR) (Weis et al., TIG 8:263-64,1992) and the method based on array is for example micro- Array (Schena et al., Science 270:467-70,1995).

It is well known in the art for the RNA conventional methods extracted, and it is public in the standard textbook of molecular biology Open, including Ausubel et al., ed., Current Protocols in Molecular Biology, John Wiley＆ Sons,New York 1987-1999.The method that RNA is extracted from paraffin-embedded tissue is disclosed in such as Rupp and Locker,Lab Invest.56:A67,(1987)；With De Andres et al., Biotechniques 18:42-44, (1995).The RNA of separation can be used for hybridization or amplification assay, and it includes but is not limited to PCR analyses and probe array.In sample The measure of intrinsic gene expression product level can also include nucleic acid amplification, for example by RT-PCR (U.S. Patent number 4,683, 202), ligase chain reaction, self training sequence is replicated, transcription amplification, rolling-circle replication and other using nucleic acid amplification method Method, the molecule then expanded using technology for detection well known to those skilled in the art.

Microarray can be used for expression analysis.Each array includes the reproducible mould for being connected to the capture probe of solid support Formula.The RNA or DNA of mark hybridize with the complementary probe on array, then pass through laser scanning inspection.Determine each to visit on array The intensity for hybridization of pin is simultaneously translated into the quantitative values for representing relative gene expression level.See, for example, U.S. Patent number 6,040, 138th, 5,800,992 and 6,020,135,6,033,860 and 6,344,316.High density oligonucleotide array can be used in particular for really A large amount of RNA gene expression profile in random sample product.

Total serum IgE for analyzing intrinsic gene set can be separated from biological sample such as tumour.If RNA source is Primary tumor, can be for example from freezing or the FFPE and the tissue sample of fixation (for example, formalin is fixed) filed RNA (such as mRNA) is extracted in (for example, tissue core sample that virologist instructs)).

Genetic analysis and data processing

For example, Patient Sample A's gene expression data from intrinsic gene set can be by the pretreatment of known technology with reality Existing sequence data is compared, the average centralization of data normalization and data.Method for normalizing includes, for example, (i) is used on array The global normalization of all genes；(ii) normalized using the house-keeping gene for the house keeper/constant gene unchangeably expressed；With (iii) the internal contrast normalization (Quackenbush of the exogenous crt gene for the known quantity added during hybridization is used Nat.Genet.32(Suppl.),496-501(2002)).Gene count estimation can also be normalized to fix quartile, example Such as fixed upper quartile.Then resulting normalization gene expression estimate can be adjusted so that in each gene It is worth the intermediate value that expression value is equal to known subset (such as the gene subset from TNBC patient).

According to an embodiment, the Patient Sample A handled by PAM50 graders expresses data first by comparing sum Pre-processed according to centralization technology.RNA sequence data are first by such as MapSplice (Nucleic Acids Res.2010Oct；38(18):e178.doi:10.1093/nar/gkq622) with people's (homo sapiens) genome sequence hg19 (https://genome.ucsc.edu/cgi-bin/hgGatewayDb=hg19) (http:// Www.ncbi.nlm.nih.gov/assembly/GCF_000001405.25/) compare.Gene and isotype level can be estimated Count, for example, using the RNA-Seq (http by expectation maximization (RSEM)://deweylab.biostat.wisc.edu/ rsem/).Gene count estimate is normalized to fixed upper quartile.Then resulting normalization base can be adjusted Because of expression estimate so that the intermediate value expression value of each gene is equal to " Comprehensive Molecular Portraits of Human Breast Tumors”,The Cancer Genome Atlas Network,Nature 490,61-70 (October 4,2012)(http://www.nature.com/nature/journal/v490/n7418/full/ Nature11412.html the median of the negative subset of the three of the TCGA RNA-seq data of report in).

After pre-processing, handled according to for handling the known technology of intrinsic gene set data from PAM50 genes battle array Patient Sample A's expression data of row.At least it is described in detail in herein below for handling from the intrinsic gene sets of PAM50 The complete explanation of Patient Sample A's gene expression data, and will only summarize and be not described in detail herein：Parker et al. .J Clin Oncol.,27(8):1160-7(2009)；U.S. Patent Application Publication No. 2011/0145176；And U.S. Patent application (U.S. Patent Application Publication No. 2013/0004482 describes PAM50 graders to be used to screen breast publication number 2013/0004482 Application of the gland cancer subject to the possibility reactivity of anthracycline therapy, it depends on and especially patient is swollen by PAM50 graders Knurl is categorized as HER2 hypotypes).It is determined that the Spearman rank correlations with substrate sample gene expression barycenter.Sample and substrate sample barycenter Between Spearman rank correlations be designated as substrate barycenter grader score.Determine and tube chamber A gene expression barycenter Spearman rank correlations.Spearman rank correlations between sample and tube chamber A barycenter are designated as tube chamber A barycenter graders Score.Then the substrate barycenter grader score so determined and tube chamber A barycenter graders score are inserted into equation,

With the substrate and tube chamber A grader scores of the weighting for providing Patient Sample A.

Sample

Sample for analyzing intrinsic Subtypes can include the biological sample containing cancer cell or tissue, such as mammary gland Tissue sample or primary breast tumor tissue sample.In some embodiments, biological sample includes breast tissue or cell. " biological sample " refers to any sampling for the cell, tissue or body fluid for being able to detect that intrinsic gene expression.Such biological sample The example of product includes but is not limited to biopsy and smear.Body fluid available for present disclosure includes blood, lymph, urine Liquid, saliva, nipple aspirate, the liquid from ductal lavage fluid, gynaecology's fluid or any other body exudates or its derivative Thing.Blood can include whole blood, blood plasma, serum or any blood derivatives.In some embodiments, biological sample includes breast Gland cell, and can especially include the breast tissue from biopsy, such as breast tumor tissue samples.Biological sample Product, for example by scraping or wiped area, can draw cell or body fluid, or pass through removal by various technologies by using pin Tissue sample (i.e. biopsy) is obtained from subject.The method for collecting various biological samples is well known in the art. In some embodiments, obtained for example, by fine needle aspiration biopsy, core needle biopsy or excisional biopsy Sample of breast tissue.In another embodiment, fluid is obtained by ductal lavage.Fine duct is inserted into the natural of ductus lactiferi Opening.Then saline solution is injected with irrigating catheter by conduit, this relaxes cell from conduit lining.Relaxation cell will be contained Solution is taken out by conduit and carries out biopsy.Fixed and staining solution can apply to cell or tissue to preserve sample Be easy to check.In one embodiment, biological sample is the sample of breast tissue for the FFPE that formalin is fixed, special It is not primary breast tumor sample.In various embodiments, tissue sample is the tissue core sample instructed from virologist What product were obtained.

Therapeutic agent

Androgen receptor inhibitor directly or indirectly suppresses androgen receptor (AR) signal path.In an embodiment In, the direct inhibitor of AR acceptors includes the miscellaneous Shandong amine of grace, Bicalutamide (Casodex), Flutamide, Nilutamide, ARN509 etc.. In another embodiment, AR indirect inhibitor includes the inhibitor of Cyp 17, such as ketoconazole, abiraterone acetate, VN/ 124-1 (TOK-001), orteronel (TAK-700) etc..In another embodiment, AR inhibitor includes Finasteride, Galeterone, CPA and andarine etc..Antigen receptor inhibitor may cause the biology of androgen receptor living The complete or partial suppression of property.

In preferred embodiments, AR inhibitor is the miscellaneous Shandong amine of graceIt has system (IUPAC) name Claim 4- (3- (4- cyano group -3- (trifluoromethyl) phenyl) -5,5- dimethyl -4- oxo -2- thiocarbamoyl imidazole quinoline -1- bases) fluoro- N- of -2- Methyl benzamide, directly in conjunction with androgen receptor (AR) and with three avtive spots.It suppresses androgen and AR combination, Suppress AR core transposition, and suppress the DNA combinations of AR mediations.

In certain embodiments, the breast cancer treatment comprising androgen receptor inhibitor is not also comprising one or more Other anticancers of androgen receptor inhibitor.This non-AR inhibitor of patient can also be given together with AR inhibitor for treating Anticancer include such as endoxan, fluorouracil (or 5 FU 5 fluorouracil or 5-FU), methotrexate (MTX), thiotepa, carboplatin is suitable Platinum, taxane, taxol, the taxol that protein is combined, docetaxel, vinorelbine, TAM, Raloxifene, Tuo Rui Meter Fen, fulvestrant, gemcitabine, Irinotecan, Ipsapirone, Temozolomide, TPT, vincristine, vinblastine, Eribulin, mutamycin, capecitabine, capecitabine, Anastrozole, Exemestane, Letrozole, Leuprorelin, A Barui Gram, Bath woods, Goserelin, megestrol acetate, Risedronate, Pamidronate, ibandronate, Alendronate, Ground promise monoclonal antibody, zoledronate, Herceptin, Lapatinib or Avastin, or its combination.

In one embodiment, non-AR inhibitor anticancer is taxol.In one embodiment, AR inhibitor is The miscellaneous Shandong amine of grace, non-AR inhibitor anticancer is taxol.As discussed below, it has also been discovered that, the combination of the miscellaneous Shandong amine of grace and taxol is led Enhanced cytotoxicity in tumour cell is caused, the cell is to the substrate by the weighting more than -0.25 and tube chamber A grader scores The prognostic marker of composition is positive.

One or more AR inhibitor of therapeutically effective amount are applied to subject according to the present invention, with using when in treatment cancer Usually used administration and therapeutic scheme treat TNBC when AR inhibitor is applied in disease.AR inhibitor can be as described herein Applied in breast cancer treatment by generally applying the approach of these medicaments.A kind of representativeness of the miscellaneous Shandong amine of such AR inhibitor grace Scheme is oral 160mg/ days, once a day.Formulation can include such as capsule.Daily dose for example can include 160mg grace The form of the capsule of miscellaneous Shandong amine is applied.In another embodiment, using four capsules, each capsule includes the miscellaneous Shandong of 40mg grace Amine.Lower or higher dosage can be used.Non- AR inhibitor used crowd when treating breast cancer according to such medicament Well known dosage and therapeutic scheme are applied.

The intrinsic gene tables of table 1-PAM50

The intrinsic gene orders of table 2-PAM50

Illustrate the practice of the present invention by following non-limiting example.

Embodiment

Embodiment 1

Clinical Study Protocol

Carry out clinical test miscellaneous Shandong amine of grace in determining its tumour as androgen receptor positive (AR+) and three negative patients The clinical benefit for the treatment of.In our current research, AR+ is defined as any core AR dyeing by immunohistochemistry (IHC), and TNBC is defined as IHC for ERs (ER) and progesterone receptor (PgR)<1% dyeing, IHC gives birth to for people's epidermis 0 or 1+ of growth factor receptor body 2 (HER2), or it is negative for the HER2 amplifications of 2+IHC diseases by situ hybridization (ISH).Pass through IHC carries out single optimization in AR dyeing, each comfortable breast cancer tissue of antibody using two kinds of different antibody.Daily oral one It is secondary to apply the miscellaneous Shandong amine (160mg/ days) of grace in the case where being with or without food with four 40mg Perles.It has recorded basis Reaction evaluation criteria (RECIST1.1) in solid tumor version 1.1 receives patient of the miscellaneous Shandong amine of grace untill progression of disease, Unless because other reason treatments specified in testing program stop.Including prescreening during research, (patient can be in its disease During any time signature agree to submit tissue carry out AR expression test)；Screening is (28 days before first dose of quantifier elimination medicine)； Treatment (the 1st day to drug withdrawal)；Security follow-up (about 30 days or starts new antineoplaston after last time dose study medicine Before, it is defined by first comer)；With the long term follow-up (life of every 3 to 6 months after the assessment and treatment drug withdrawal of subsequent breast cancer treatment Deposit state).Objective reaction-reacting (CR) or partial reaction (PR) completely-is determined by researcher according to RECIST 1.1.

The experiment is the research of the stages of Simon 2, wherein research is expanded to it is more extensive before, in predefined patient Minimum benefit is needed in colony.In the 1st stage, 42 patients participate in research can assess patient to obtain predetermined 26. The necessary clinical benefit for proceeding to for the 2nd stage is observed in the 1st stage, other 76 patients are recruited, altogether 118 patients.Connect It is excluded by the patient shifted with central nervous system (CNS) of the prior treatment of androgen receptor signal transduction inhibitor Outside；Quantity to prior treatment is not limited, and the patient with the immeasurablel disease of measurable disease or only bone is that have Qualification.16 weeks clinical benefit rate (CBR16) be defined as complete incidence graph (CR), part and alleviate (PR) or stable type disease (SD) The ratio for assessing patient of the optimum response of >=16 weeks (CBR16).It also have evaluated the clinical benefit rate (CBR16) of >=24 weeks.

In the stage 1,42 patients are recruited to obtain 26 evaluable patients (n=26).Appreciable patient be There is the patient that AR is dyed after >=10% tumour and at least 1 time baseline in tumor evaluation.Treatment of purpose (ITT) crowd's (the 1st rank Section n=42) it is defined as central evaluation AR+TNBC and receives all recruitments of at least 1 dose quantifier elimination medicine Patient.It is appreciable to have 26 (62%) in 42 ITT patients, has 16 can not assess in 42.It is being unsatisfactory for assessing mark In accurate 16,10 AR having less than 10% are expressed；6 AR with >=10% are expressed, but are commented after no progress baseline Estimate and (find that 2 there are CNS transfers soon after research enters, and removed before tumor evaluation after carrying out baseline from treatment Go out).Patient more than 50% receive the miscellaneous Shandong amine of grace as its first or second line treatment, and before the miscellaneous Shandong amine treatment of grace is received,> 30% patient has >=3 previous schemes.

Intrinsic gene expression analysis

Human breast cancer from TNBC patient is obtained from the clinical research of the foregoing miscellaneous Shandong amine of AR antagonist grace.Patient Dyeing is expressed for AR by breast cancer tissue.Patient's dyeing is by virologist according to staining power (3+, 2+ and 1+) and in standard The tumour cell percentage of the dyeing provided in operation sequence is classified.AR dyes are all have evaluated in nucleus and cytoplasm Color.

The RNA-seq data used in this research are carried out as follows pretreatment.By RNA-seq data with coming from human genome People's (homo sapiens) genome sequence hg19 (hg19 created by UC Santa Cruz genome bioinformatics group of browser Assembly (https://genome.ucsc.edu/cgi-bin/hgGatewayDb=hg19) (http:// Www.ncbi.nlm.nih.gov/assembly/GCF_000001405.25/)) using MapSplice (Nucleic Acids Res.2010Oct；38(18):e178.doi:10.1093/nar/gkq622) be compared.Using passing through expectation maximization RNA-Seq(RSEM)(http://deweylab.biostat.wisc.edu/rsem/) estimate gene and isotype leveler Number.Gene count estimate is normalized to fixed upper quartile.Normalization gene expression estimate obtained by adjustment, So that the intermediate value expression value of each gene is equal to " Comprehensive Molecular Portraits of Human Breast Tumors”,The Cancer Genome Atlas Network,Nature 490,61-70(October 4, 2012)(http://www.nature.com/nature/journal/v490/n7418/full/nature11412.html) The median of the negative subset of the three of the TCGA RNA-seq data of middle report.

Use Parker et al. .J Clin Oncol., 27 (8):The PAM50 disaggregated models of 1160-7 (2009) descriptions will Intrinsic Subtypes proceed in LumA, LumB, substrate, HER2 and normal group.To the Fu Er collected from subject's tumor of breast The genomic data that the RNA sequencings for the RNA that the paraffin-embedded tissue that Malin fixes is obtained are obtained carries out intrinsic Subtypes.Data Pre-processed as described above.Subtypes are carried out on " training and test " collection and further " checking " collection.Instruction Practice and test set is made up of 122 Patient Sample As, wherein 42 patients come from prescreening crowd, but have neither part nor lot in research, 80 trouble Recruitment crowd of person's sample in clinical research.Checking collection is made up of 55 Patient Sample As, wherein 15 patients come from and do not joined With the prescreening crowd of research, 40 crowds of the sample from recruitment.

The method point of the intrinsic gene set data of PAM50 is analyzed according to known being used for as described in Parker et al. (ibid) Analyse data.Substantially, carry out the detection of the expression of 50 hypotype predicted gene collection of the table 1 from patient tumor samples and estimate Meter.Analysis provides 50 hypotype predicted gene collection of the methods described of substrate sample, HER2, LumA, LumB and normal Subtypes Express spectra.To each sample and PAM50 centroid calculation Spearman correlations.These values are used as sample and each barycenter The continuous estimation of distance or similarity.The hypotype of each sample is assigned to closest to (maximum positive correlation) barycenter.Using with it is every The fundamental measurement of the correlation of individual hypotype classifies sample as one of 4 kinds of tumors subtypes (substrate sample, HER2, LumA and LumB) Or normal sample.

In addition, have evaluated the Spearman rank correlations with substrate sample gene expression barycenter.Sample and substrate sample barycenter it Between Spearman rank correlations be designated as " substrate barycenter grader score ".It has evaluated and tube chamber A gene expression barycenter Spearman rank correlations.Spearman rank correlations between sample and tube chamber A barycenter are designated as that " tube chamber A graders are obtained Point ".

In patient (treatment of purpose (ITT)) colony of recruitment, nothing of the substrate sample hypotype generally with being treated to the miscellaneous Shandong amine of grace Reaction is related, and the presence of one of other hypotypes is generally related to the reaction treated to the miscellaneous Shandong amine of grace.Referring to Fig. 1, wherein " examining Disconnected-" substrate sample subgroups are represented, " diagnosis+" represents the patient of Her2, LumA, LumB or normal hypotype.Therefore, represent non- The PAM50 gene expressions classification device result of substrate sample tumor type is for predicting the reaction treated to the miscellaneous Shandong amine of grace in TNBC Mark.

Embodiment 2

The clinical study results of embodiment 1 are further analyzed using patient's substrate barycenter grader score.Utilize substrate matter A series of threshold cutoff values of heart grader score have evaluated therapeutic response data.Using 0.2,0.3,0.4,0.5,0.6,0.65, 0.7th, the miscellaneous Shandong amine reaction/reactionless data of 0.8 and 0.9 substrate barycenter grader score cutoff value analysis grace.Data such as Fig. 2A/ Shown in B to 10A/B.In each figure, " diagnosis+" represents that its sample meets the specified prognosis characterizations including specifying threshold cutoff value Patient." diagnosis-" represents that its sample is unsatisfactory for specifying the patient of threshold cutoff value.

As shown in Fig. 2A/B-10A/B, the 0.6 or lower target substrate barycenter grader for defining Dx+ and Dx- patients Score is most related to the reaction treated to the miscellaneous Shandong amine of grace, and is omited based on the predictive value that 0.2 to 0.9 score defines Dx+ and Dx- It is low.Therefore, according in the range of 0.2-0.9 substrate barycenter grader cutoff value score define the group of reactor and non-reactor Body is for predicting the further basis of reactivity treated in TNBC to the miscellaneous Shandong amine of grace, 0.6 or lower substrate matter of sample Heart grader score is the preferred embodiment for predicting the mark of reactivity.As shown in Figure 6A, according to 0.6 relative base Substrate heart grader score define Dx+ and Dx- cause to produce the big diagnosis with most of reactors in diagnosis+colony+ The prediction of high nonresponder in colony and diagnosis-crowd.

Embodiment 3

Further analysis and summary were as shown in figure 11 for the clinical study results of embodiment 1, it is shown that in the clinic of >=24 weeks The reaction that various patient's subgroups are treated to the miscellaneous Shandong amine of grace in terms of earning rate (CBR24).Subgroup is suffered from including institute's intention to treat (ITT) Person；Appreciable patient；Breast tumor tissues patient (the IHC AR of AR dyeing >=10%>=10%)；Pass through PAM50 hypotypes point Breast tumor tissues are categorized as the patient (non-substrate PAM50) of non-substrate sample hypotype by class device；Staging is substrate sample hypotype Patient (substrate PAM50)；Pass through application<0.6, >=0.6,<0.7, >=0.7,<0.75 and >=0.75 specified cutoff value is from base Substrate heart grader score is come the Patient Sample A that is analyzed." DX- " represents that sample is unsatisfactory for specifying the patient of threshold cutoff value. " DX+ " represents that sample meets the patient for specifying threshold cutoff value.It also show in Figure 11 and meet combination standard IHC AR>=10% He DX+<The data of 0.6 sample, i.e. sample meet the AR dyeing of (i) more than 10% and (ii) 0.6 or lower PAM50 gene tables Up to the standard of substrate barycenter grader score.

Embodiment 4

Further analysis and summary were as shown in figure 12 for the clinical study results of embodiment 1, it is shown that in the clinic of >=24 weeks The reaction that various patient's subgroups are treated to the miscellaneous Shandong amine of grace in terms of earning rate (CBR24).Subgroup is suffered from including institute's intention to treat (ITT) Person；Appreciable patient；Breast tumor tissues patient (the IHC AR of AR dyeing >=10%>=10%)；With the treatment of grace miscellaneous Shandong amine It is used as independent (First Line) or the patient of second (the second line) treatment.Subgroup further comprises by application<0.6 substrate barycenter Patient Sample A's subgroup that grader score cutoff value is analyzed (" Novel DX+ "), and comprising from the first and second lines The subgroup of the sample for the treatment of, application<0.6 cutoff value.Use<42% CBR of 0.6 prognosis substrate barycenter grader score (being 60% when being used in the group comprising both the first and second line patients) has exceeded for predicting in TNBC to treatment The typical reference of reactivity, the prediction energy with the model of the reaction for predicting the hormone agents treatment to ER+/PgR+ breast cancer Power is the same.

Embodiment 5

Utilize<0.6 substrate barycenter grader score is used as the new of the predictive factor of the reaction to AR inhibitor for treating Patient of the effect of prognosis characterizations further in fig. 13 on 56 weeks shows the Progression free survival time.As a result show, with >=0.6 compares apart from patient's (" Novel DX Neg ") of score, is accredited as meeting<0.6 substrate barycenter grader score New prognosis characterizations condition patient's (" Novel DX Pos ") in progression free survival phase.

Embodiment 6

The clinical research knot of embodiment 1 is further analyzed using patient's substrate barycenter grader and tube chamber A graders score Really.Analyze grader score and response data.As the result of analysis, substrate and the tube chamber A classification of weighting are empirically devised Device score, it predicts the reactivity treated to androgen receptor inhibitor in clinical test.The substrate of the weighting of Patient Sample A Determined with tube chamber A grader scores by below equation：

Then therapeutic response data are assessed using the substrate of weighting and a series of threshold cutoff values of tube chamber A grader scores. Specifically, using more than -0.2, more than -0.25, the substrate and tube chamber A graders of the weighting more than -0.3 and more than -0.35 Score cutoff value analyzes grace miscellaneous Shandong amine reaction/non-response data.Data such as Figure 14 A (>- 0.2), 14B (>- 0.25), 14C (>- 0.3) and 14D (>- 0.35) shown in.In each figure, " diagnosis+" represents that its sample meets the finger for including specifying threshold cutoff value Determine the patient of prognosis characterizations." diagnosis-" represents that its sample is unsatisfactory for specifying the patient of threshold cutoff value.

As shown in Figure 14 A-14D, (wherein x is -0.2 for the substrate of weighting of the selection more than x and the standard of tube chamber A graders In the range of to -0.3) it is most preferably related to the reaction treated to the miscellaneous Shandong amine of grace, wherein the score criteria more than -0.25 is optimal 's.Therefore, substrate and tube chamber A grader scores based on the weighting more than -0.2 or more than -0.3 define reactor and non-reaction The colony of person is to predict the reactive basis treated in TNBC to the miscellaneous Shandong amine of grace, wherein the substrate of weighting more than -0.25 and Tube chamber A grader scores are the preferred embodiments for predicting the standard of reactivity.

Embodiment 7

The result of the clinical research of embodiment 1 was further analyzed and summarized in fig .15, it is shown that in the clinic of >=24 weeks The reaction that various patient's subgroups are treated to the miscellaneous Shandong amine of grace in terms of earning rate (CBR24).Subgroup is suffered from including institute's intention to treat (ITT) Person；Appreciable patient；Pass through application>- 0.2,>- 0.25,>- 0.3 and>- 0.35 specified cutoff value in weighting substrate and Tube chamber A graders score analyzes the patient of breast tumor tissue samples." PR-AR DX- " represent that sample is unsatisfactory for specifying threshold to cut The patient of disconnected value." PR-AR DX+ " represent that sample meets the patient for specifying threshold cutoff value.Thus, for example, " PR-AR DX+>- 0.25 " represents that sample meets the patient of the standard of substrate and tube chamber A graders score more than -0.25 of weighting.

Also illustrate that (i) is not receiving or received once to be used for the non-androgen receptor inhibitor that TNBC is treated in fig .15 Medicine prior treatment (" and 0-1 prior treatment ") afterwards or (ii) receiving for TNBC treat non-androgen receptor The medicine of inhibitor two or more times prior treatment (" and>=2 prior treatments ") it is followed by being ground by the miscellaneous Shandong amine treatment of grace The response data of the sample of patient in studying carefully.These Patient Sample As are applied>The substrate and tube chamber A graders of -0.25 weighting Score cutoff value.

Embodiment 8

Use>The substrate of -0.2 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating is further illustrated the Progression free survival time on the patient of 56 weeks in figure 16. As a result show and be accredited as the substrate and tube chamber A graders score (" PR-AR DX+ that meet the weighting more than -0.2：>- 0.2 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.2：<=-0.2 ", bottom curve) Prognosis characterizations condition patient in extension progression free survival phase.

Embodiment 9

Use>The substrate of -0.25 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating is further illustrated the Progression free survival time on the patient of 56 weeks in fig. 17. As a result show and be accredited as the substrate and tube chamber A graders score (" PR-AR DX+ that meet the weighting more than -0.25：>- 0.25 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.25：<=-0.25 ", bottom is bent Line) prognosis characterizations condition patient in extension progression free survival phase.

Embodiment 10

Use>The substrate of -0.3 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating is further illustrated the Progression free survival time on the patient of 56 weeks in figure 18. As a result show and be accredited as the substrate and tube chamber A graders score (" PR-AR DX+ that meet the weighting more than -0.3：>- 0.3 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.3：<=-0.3 ", bottom curve) Prognosis characterizations condition patient in extension progression free survival phase.

Embodiment 11

Use>The substrate of -0.35 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating was further illustrated the Progression free survival time in Figure 19 on the patient of 56 weeks. As a result show and be accredited as the substrate and tube chamber A graders score (" PR-AR DX+ that meet the weighting more than -0.35：>- 0.35 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.35：<=-0.35 ", bottom is bent Line) prognosis characterizations condition patient in extension progression free survival phase.

Embodiment 12

Use>The substrate of -0.25 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating in fig. 20 on patient's Progression free survival time of 56 weeks not receiving or Receiving once is used to further show in the patient of the prior treatment of the medicine for the non-androgen receptor inhibitor that TNBC is treated. As a result show and be accredited as the substrate and tube chamber A graders score (" PR-AR DX+ that meet the weighting more than -0.25：>- 0.25 ", top curve) relative to grader score (" the PR-AR DX- less than or equal to -0.25：<=-0.25 ", bottom is bent Line) characteristic condition patient in extension progression free survival phase.- 0.25 section is relatively appreciated that from Figure 17 and Figure 20 Disconnected value can identification mark be longer Progression free survival duration (Figure 20) of 0 to 1 prior treatment group, relative to spy Levy the shorter Progression free survival duration (Figure 17) for being the colony of all research patients.

Use>The substrate of -0.25 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating is not receiving or received once to be used for the non-hero that TNBC is treated in fig 23 Further shown in the patient of the prior treatment of the medicine of hormone receptor inhibitor.Figure 23 is similar to Figure 20, except in research The Progression free survival time is confirmed as 64 weeks of 56 weeks more than Figure 20 into Figure 23.

Embodiment 13

Use>The substrate of -0.25 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating is in Figure 21 A and 21B on not receiving or receiving once (0-1 elder generation Preceding treatment) or two or more times (2+ prior treatment) be used for TNBC treat non-androgen receptor inhibitor medicine elder generation The treatment time that gets nowhere of the patient of preceding treatment further shows.It is accredited as meeting the substrate and pipe of the weighting more than -0.25 56 patients of the characteristic condition of chamber A grader scores show in Figure 21 B.Obtained by the grader less than or equal to -0.25 62 research patients of identification are divided to be accredited in Figure 21 A.Each bar in figure represents a patient.Receiving once or do not having It is that obvious (Figure 21 B) indicates triangle to have the golden hour without progression of disease in the reactor for receiving prior treatment Patient's bar is active (" active ") under study for action.The patient's bar for indicating asterisk represents to react (CR) or partial reaction completely (PR)。

Embodiment 14

Use>The substrate of -0.25 weighting and the new prognosis characterizations of tube chamber A grader score cutoff values press down as to AR The effect of the predictive factor of the reaction of preparation for treating (was schemed in Figure 22 A and 22B on patient's Progression free survival time of 64 weeks 22A) Overall survival (Figure 22 B) with 84 weeks is further shown.Figure 22 A result show be accredited as meet be more than- The substrate and tube chamber A graders score (" PR-AR DX+ of 0.25 weighting：>- 0.25 ", top curve) relative to being less than or wait In -0.25 grader score (" PR-AR DX-：<=-0.25 ", bottom curve) prognosis characterizations condition patient in prolong Long progression free survival phase.Figure 22 B result, which is shown, is being accredited as meeting the substrate and tube chamber A of the weighting more than -0.25 Grader score (" PR-AR DX+：>- 0.25 ", top curve) relative to grader the score (" PR- less than or equal to -0.25 AR DX-：<=-0.25 ", bottom curve) prognosis characterizations condition patient in extension progression free survival phase.It is unsatisfactory for pre- Afterwards the patient of characteristic condition be characterized in 8.1 weeks middle position progression free survival phase and the middle position Overall survival of 32.1 weeks.Compared to it Under, the patient for meeting prognosis characterizations condition is characterised by the middle position progression free survival phase of 16.1 weeks, and and not yet reach within 84 weeks To middle position Overall survival.

Embodiment 15

It has been reported that the II clinical trial phases of androgen receptor antagonists Bicalutamide.Ayca et al., " Phase II Trial of Bicalutamide in Patients with Androgen Receptor Positive,Hormone Receptor Negative Metastatic Breast Cancer”,Clin Cancer Res 19:5505-5512 (October 1,2013).It is negative and pregnant that the experiment is designed to the research Bicalutamide treatment AR positives, ERs (ER) The curative effect of the negative metastatic breast cancer of hormone receptor (PgR).

In brief, as described in Ayca et al., by immunohistochemistry (IHC) (>10% nuclear staining is considered as positive ) AR is intensively tested to the tumour from the negative advanced breast cancer patients of 452 ER feminine genders/PgR.Extra eligibility criteria ginseng See Ayca et al., page 5506.If primary or metastasis site is the positive, patient meets qualification with daily 150mg dosage Receive AR antagonist Bicalutamides.28 treatment patients under study for action.Orally administered according to continuous daily scheme than card Shandong Amine 150mg.Patient is treated until progression of disease or unacceptable adverse events.Allow most 2 dosage of >=3 grades of toxicity Reduce (100 and 50mg).Due to toxicity, treatment delay can at most allow 2 weeks.Two are removed from research and takes Bicalutamide Patient, leave 26 suffer from AR (+) ER/PgR (-) metastatic breast cancer research participants.5 patient experiences stable diseases>6 Month (the periodicity of completion：6,8,10+, 13,57+), this is its preferably reaction to treatment.In the presence of the complete or portion of no confirmation Divide reaction, the clinical benefit rate for causing target group is 19% (95%CI, 7%-39%) (n=26).In purpose Treatment analysis In, it was observed that 18% (95%CI, 6%-37%) CBR.Referring to Ayca et al., page 5507.

21 in the research patient of 26 Bicalutamide treatments are determined being also HER-2 negative, i.e., 21 patients have Triple negative breast cancer (Her-2 (-), ER (-) and progesterone receptor PgR (-)).Result of study shows, makes to receive Bicalutamide to control The patient tumor samples of the 21 TNBC patients treated have carried out the tube chamber A, tube chamber B, substrate using PAM50 parting models The intrinsic Subtypes of sample, HER2 enrichments and normal sample group.Each hypotype score of each sample is listed in Table 3 below.Also arranged in table 3 The substrate and tube chamber A grader scores of the weighting of each sample are gone out.Clinical test based on the miscellaneous Shandong amine of AR- receptor antagonist grace Embodiment 6 in the result that obtains, the substrate and tube chamber A graders score (" PR-AR DX+ of the weighting more than -0.25>- 0.25 ") show that such patient is more likely more right than the patient that substrate and tube chamber A the classification score of weighting are less than or equal to -0.25 Bicalutamide treatment reacts.8 patients meet the standard, and are appointed as in table 3 the amine treatment of contrast card Shandong and may have sun Property (" POS ") prognosis.The confidence level of each display 1 in 21 Patient Sample As, in addition to sample 16, its confidence level For 0.99.

Table 3

Embodiment 16

Research shows below, positive in the substrate of the weighting more than -0.25 and the prognostic marker of tube chamber A grader scores Cell in, the miscellaneous Shandong amine of grace adds the combination of taxol to have enhanced antitumor action.

Triple negative breast cancer cell line BT549, MDA-MB-436, MDA-MB-453 is selected to be studied.The letter of cell line RNA data sets are made to be downloaded from encyclopaedical (CCLE) database of cancerous cell line.Each cell is determined from the database of download The substrate and tube chamber A grader scores of the weighting of system.Using>The substrate and tube chamber A grader scores of -0.25 weighting are as right The reactive prognostic marker of AR inhibitor for treating, determines MDA-MB-453 but is not that BT549 and MDA-MB-436 meet should Standard.

Cell is maintained in 10%FBS supplement growth mediums.Vitality test is carried out in 10%FBS, and according to system The scheme (Promega) for making business uses CellTiter-Glo reagent measurings.It is individually or miscellaneous with the grace of Paclitaxel combinations in order to determine Shandong amine is to the molecular effect of androgen receptor signal transduction, by cell (BT549, MDA-MB-436 or MDA-MB-453) the 1st It is inoculated with 10%FBS.Cell is located with the miscellaneous Shandong amine of grace or taxol or the two combination (in 2% charcoal handles serum) Reason, and stimulated 4 hours with 10nM DHT.For kytoplasm and core fraction separation Cell Fractionation.Egg is determined using western blot method White matter expression.For each cell line, the IC of the miscellaneous Shandong amine of grace or taxol₅₀As shown in table 4.Given for each cell line Average value (n=3).Compared with the negative BT549 and MDA-MB-463 cells of prognostic marker, the positive MDA- of prognostic marker MB-453 cells show higher sensitiveness to the miscellaneous Shandong amine of grace.

Table 4

Cell line	The miscellaneous Shandong amine IC of grace₅₀(μM)	Taxol IC₅₀(nM)
			BT549	57.0	2.8
MDA-MB-436	73.0	6.7
			MDA-MB-453	22.7	20.7

The miscellaneous Shandong amine (Enza) of grace in Figure 24 A-C and the vigor that cell is measured in the presence of the concentration of taxol (PTX). Average value (n=5) is presented for each cell line.In the positive MDA-MB-453 cell lines of prognostic marker, the miscellaneous Shandong amine of grace Plus the combination of taxol causes enhanced cytotoxicity.Referring to Figure 24 C.

Embodiment 17

In order to produce mice xenograft model, by the female NOD-SCID mouse and 6.0x10 of 5 to 6 week old⁶Individual MDA- MB-453 cell in-situs are expelled in mammary gland.By DHT (10.5mg in 60 days release pills) or control pill implantation animal body It is interior.When tumor size reaches~100mm³When, feed the miscellaneous Shandong amine of (PO) grace by (i) with 3mg/kg/ days (n=10) mouths (" Enza "), (ii) feeds taxol (" PTX "), or (iii) (i) and (ii) (n=10) with 6mg/kg QMWF (IP) (n=7) mouth Combined treatment mouse.With medium (0.5%Methocel solution) processing control group mice (n=8).Tumor size slide calliper rule Measurement.Tumor weight was determined at the 35th day.As a result Figure 25 A (gross tumor volume relative time) and Figure 25 B (tumor weight) are shown in.Figure Data point in 25A represents every group of mean tumour volume, and error bars reflect the SEM of data.Student T- is examined for calculating p Value：Figure 25 A：The miscellaneous Shandong amine of the relative grace of control, 0.007；The relative taxol of control, 0.0007；The miscellaneous Shandong amine of grace adds with respect to the miscellaneous Shandong amine of grace Taxol, 0.074；Taxol adds taxol, 0.013 with respect to the miscellaneous Shandong amine of grace.Figure 25 B：The miscellaneous Shandong amine of the relative grace of control, 0.001；It is right Photograph is to taxol, 0.0001；The miscellaneous Shandong amine of grace adds taxol, 0.08 with respect to the miscellaneous Shandong amine of grace；Taxol adds purple with respect to the miscellaneous Shandong amine of grace China fir alcohol, 0.017.As shown by data, compared with both medicines are used alone, it is enhanced that the miscellaneous Shandong amine of grace adds the combination of taxol to cause Antitumous effect.

The representative tumour from each treatment group is selected to carry out the immunohistochemistry for AR, Ki67 or p-AKT. Compared with the miscellaneous Shandong amine of grace or taxol single therapy group, the miscellaneous Shandong amine of grace adds the immune of Ki67 or AKT phosphorylations in taxol tumour Histochemical stain is significantly reduced (data are not shown).

The disclosure of herein cited each patent, patent application and publication is incorporated herein by reference in their entirety.This Art personnel will readily appreciate that, the present invention be perfectly suitable for realizing purpose and obtain mentioned objects and advantages with And wherein intrinsic objects and advantages.Although disclosing the present invention by reference to specific embodiment, but it is clear that this area skill Art personnel can be designed that other embodiments of the present invention and modification, without departing from the true spirit of the practice for the present invention And scope.Appended claims are intended to be interpreted as including all these embodiments and equivalent variations.

Sequence table

<110> MEDIVATION PROSTATE THERAPEUTICS, INC.

<120>The method predicted the method for the reaction to breast cancer treatment agent and treat breast cancer

<130> 212181-0001-00-WO

<150> US 62/091,195

<151> 2014-12-12

<150> US 62/142,504

<151> 2015-04-03

<150> US 62/167,110

<151> 2015-05-27

<160> 151

<170> PatentIn version 3.5

<210> 1

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 1

aaagattcct gggacctga 19

<210> 2

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 2

acagccactt tcagaagcaa g 21

<210> 3

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 3

ctggaagagt tgaataaaga gc 22

<210> 4

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 4

tacctgaacc ggcacctg 18

<210> 5

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 5

gcacaaagcc attctaagtc 20

<210> 6

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 6

gctggctgag cagaaag 17

<210> 7

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 7

ctttcgcctg agcctattt 19

<210> 8

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 8

ggccaaaatc gacaggac 18

<210> 9

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 9

ctgtctgagt gccgtggat 19

<210> 10

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 10

gtaaatcacc ttctgagcct 20

<210> 11

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 11

ggaggcggaa gaaaccag 18

<210> 12

<211> 24

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 12

gacaaggaga atcaaaagat cagc 24

<210> 13

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 13

gtggcagcag atcacaa 17

<210> 14

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 14

cctcacgaat tgctgaactt 20

<210> 15

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 15

catgaaatag tgcatagttt gcc 23

<210> 16

<211> 25

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 16

acacagaatc tatacccacc agagt 25

<210> 17

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 17

gctggctctc acactgatag 20

<210> 18

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 18

gcagggagag gagtttgt 18

<210> 19

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 19

cccatccatg tgaggaagta taa 23

<210> 20

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 20

cttcttggac cttggcg 17

<210> 21

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 21

gctactacgc agacacg 17

<210> 22

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 22

gatgttcgag tcacagagg 19

<210> 23

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 23

ttcggctgga aggaacc 17

<210> 24

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 24

cgtggcagat gtgaacga 18

<210> 25

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 25

ggagatccgt caactccaaa 20

<210> 26

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 26

tgggtcgtgt caggaaac 18

<210> 27

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 27

cgcagtcatc cagagatgtg 20

<210> 28

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 28

actcagtaca agaaagaacc g 21

<210> 29

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 29

gttggaccag tcaacatctc tg 22

<210> 30

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 30

tgtggctcat taggcaac 18

<210> 31

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 31

gactccaagc gcgaaaac 18

<210> 32

<211> 24

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 32

ccaacaaaat attcatggtt cttg 24

<210> 33

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 33

ccagtagcat tgtccgag 18

<210> 34

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 34

gtctctggta atgcacact 19

<210> 35

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 35

gtggaatgcc tgctgacc 18

<210> 36

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 36

aggggtgccc tctgagat 18

<210> 37

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 37

cgagatcgcc aagatgtt 18

<210> 38

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 38

aggcgaacac acaacgtc 18

<210> 39

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 39

agcctcgaac aattgaaga 19

<210> 40

<211> 27

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 40

atcgactgtg taaacaacta gagaaga 27

<210> 41

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 41

tttaagaggg caatggaagg 20

<210> 42

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 42

tgccgcagaa ctcacttg 18

<210> 43

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 43

cctcagatga tgcctatcca 20

<210> 44

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 44

cagcaagcga tggcatagt 19

<210> 45

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 45

aatgccaccg aagcctc 17

<210> 46

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 46

tcgaactgaa ggctatttac gag 23

<210> 47

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 47

gtcgaagccg caattagg 18

<210> 48

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 48

caaacgtgtg ttctggaagg 20

<210> 49

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 49

tgccctgtat gatgtcagga 20

<210> 50

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 50

gtgaggggtg tcagctcagt 20

<210> 51

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 51

tggggcagtt ctgtattact tc 22

<210> 52

<211> 24

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 52

cgatggtttt gtacaagatt tctc 24

<210> 53

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 53

gcaaatcctt gggcaga 17

<210> 54

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 54

gccgtacagt tccacaaagg 20

<210> 55

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 55

gacgcttcct atcactctat tc 22

<210> 56

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 56

ttcctccatc aagagttcaa ca 22

<210> 57

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 57

gggcacatcc agatgttt 18

<210> 58

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 58

gggtctgcac agactgcat 19

<210> 59

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 59

tccttgtaat ggggagacca 20

<210> 60

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 60

acttgggata tgtgaataag acc 23

<210> 61

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 61

ggggaaagac aaagtttcca 20

<210> 62

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 62

actgtctggg tccatggcta 20

<210> 63

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 63

ggatttcgtg gtgggttc 18

<210> 64

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 64

ccacagtctg tgataaacgg 20

<210> 65

<211> 24

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 65

ccatcaacat tctctttatg aacg 24

<210> 66

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 66

atcaactccc aaacggtcac 20

<210> 67

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 67

gcccttacac atcggagaac 20

<210> 68

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 68

gacttcaggg tgctggac 18

<210> 69

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 69

tgtgaagcca gcaatatgta tc 22

<210> 70

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 70

tattgggagg caggaggttt a 21

<210> 71

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 71

ctgagttcat gttgctgacc 20

<210> 72

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 72

gacagctact attcccgtt 19

<210> 73

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 73

tatgtgagta agctcggaga c 21

<210> 74

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 74

agtgggcatc ccgtaga 17

<210> 75

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 75

agtggacatg cgagtggag 19

<210> 76

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 76

caccgctgga aactgaac 18

<210> 77

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 77

cgtgcacatc catgacctt 19

<210> 78

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 78

gaggagatga ccttgcc 17

<210> 79

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 79

gccatagcca ctgccact 18

<210> 80

<211> 17

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 80

cttcgactgg actctgt 17

<210> 81

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 81

cagacatgtt ggtattgcac att 23

<210> 82

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 82

aggcgatcct gggaaattat 20

<210> 83

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 83

cccatttgtc tgtcttcac 19

<210> 84

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 84

ctgatggttg aggctgtt 18

<210> 85

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 85

cgcactccag cacctagac 19

<210> 86

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 86

tcacagggtc aaacttccag t 21

<210> 87

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 87

gatggtagag ttccagtgat t 21

<210> 88

<211> 18

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 88

tctggtcacg cagggcaa 18

<210> 89

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 89

acacagatga tggagatgtc 20

<210> 90

<211> 25

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 90

agtagctaca tctccaggtt ctctg 25

<210> 91

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 91

cggattttat caacgatgca g 21

<210> 92

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 92

catttgccgt ccttcatcg 19

<210> 93

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 93

gcaggtcaaa actctcaaag 20

<210> 94

<211> 20

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 94

agcgggcttc tgtaatctga 20

<210> 95

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 95

gcctcagatt tcaactcgt 19

<210> 96

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 96

ctgctgagaa tcaaagtggg a 21

<210> 97

<211> 19

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 97

ggaacaaact gctctgcca 19

<210> 98

<211> 22

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 98

acagctcttt agcatttgtg ga 22

<210> 99

<211> 23

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 99

gggactatca atgttgggtt ctc 23

<210> 100

<211> 21

<212> DNA

<213>Artificial sequence

<220>

<223>The primer of chemical synthesis

<400> 100

cacacagttc actgctccac a 21

<210> 101

<211> 2199

<212> DNA

<213>Homo sapiens

<400> 101

cagcggcgct gcggcggctc gcgggagacg ctgcgcgcgg ggctagcggg cggcggagcg 60

gacggcgacg gggcgctctc gggctgccgg cggggccgag cgccgcgcgt cccgagcatg 120

gcaggctccc tgcctccctg cgtggtggac tgtggcaccg ggtataccaa gcttggctac 180

gcaggcaaca ctgagcccca gttcattatt ccttcatgta ttgccatcag agagtcagca 240

aaggtagttg accaagctca aaggagagtg ttgaggggag ttgatgacct tgactttttc 300

ataggagatg aagccatcga taaacctaca tatgctacaa agtggccgat acgacatgga 360

atcattgaag actgggatct tatggaaagg ttcatggagc aagtggtttt taaatatctt 420

cgagctgaac ctgaggacca ttatttttta atgacagaac ctccactcaa tacaccagaa 480

aacagagagt atcttgcaga aattatgttt gaatcattta acgtaccagg actctacatt 540

gcagttcagg cagtgctggc cttggcggca tcttggacat ctcgacaagt gggtgaacgt 600

acgttaacgg ggatagtcat tgacagcgga gatggagtca cccatgttat cccagtggca 660

gaaggttatg taattggaag ctgcatcaaa cacatcccga ttgcaggtag agatattacg 720

tatttcattc aacagctgct aagggagagg gaggtgggaa tccctcctga gcagtcactg 780

gagaccgcaa aagccattaa ggagaaatac tgttacattt gccccgatat agtcaaggaa 840

tttgccaagt atgatgtgga tccccggaag tggatcaaac agtacacggg tatcaatgcg 900

atcaaccaga agaagtttgt tatagacgtt ggttacgaaa gattcctggg acctgaaata 960

ttctttcacc cggagtttgc caacccagac tttatggagt ccatctcaga tgttgttgat 1020

gaagtaatac agaactgccc catcgatgtg cggcgcccgc tgtataagaa tgtcgtactc 1080

tcaggaggct ccaccatgtt cagggatttc ggacgccgac tgcagaggga tttgaagaga 1140

gtggtggatg ctaggctgag gctcagcgag gagctcagcg gcgggaggat caagccgaag 1200

cctgtggagg tccaggtggt cacgcatcac atgcagcgct acgccgtgtg gttcggaggc 1260

tccatgctgg cctcgactcc cgagttcttt caggtctgcc acaccaagaa ggactatgaa 1320

gagtacgggc ccagcatctg ccgccacaac cccgtctttg gagtcatgtc ctagtgtctg 1380

cctgaacgcg tcgttcgatg gtgtcacgtt ggggaacaag tgtccttcag aacccagaga 1440

aggccgccgt tctgtaaata gcgacgtcgg tgttgctgcc cagcagcgtg cttgcattgc 1500

cggtgcatga ggcgcggcgc gggcccttca gtaaaagcca tttatccgtg tgccgaccgc 1560

tgtctgccag cctcctcctt ctcccgccct cctcaccctc gctctccctc ctcctcctcc 1620

tccgagctgc tagctgacaa atacaattct gaaggaatcc aaatgtgact ttgaaaattg 1680

ttagagaaaa caacattaga aaatggcgca aaatcgttag gtcccaggag agaatgtggg 1740

ggcgcaaacc cttttcctcc cagcctattt ttgtaaataa aatgtttaaa cttgaaatac 1800

aaatcgatgt ttatatttcc tatcattttg tattttatgg tatttggtac aactggctga 1860

tactaagcac gaatagatat tgatgttatg gagtgctgta atccaaagtt tttaattgtg 1920

aggcatgttc tgatatgttt ataggcaaac aaataaaaca gcaaactttt ttgccacatg 1980

tttgctagaa aatgattata ctttattgga gtgacatgaa gtttgaacac taaacagtaa 2040

tgtatgagaa ttactacaga tacatgtatc ttttagtttt ttttgtttga actttctgga 2100

gctgttttat agaagatgat ggtttgttgt cggtgagtgt tggatgaaat acttccttgc 2160

accattgtaa taaaagctgt tagaatattt gtaaatatc 2199

<210> 102

<211> 1989

<212> DNA

<213>Homo sapiens

<400> 102

cagcggcgct gcggcggctc gcgggagacg ctgcgcgcgg ggctagcggg cggcggagcg 60

gacggcgacg gggcgctctc gggctgccgg cggggccgag cgccgcgcgt cccgagcatg 120

gcaggctccc tgcctccctg cgtggtggac tgtggcaccg ggtataccaa gcttggctac 180

gcaggcaaca ctgagcccca gttcattatt ccttcatgta ttgccatcag agagtcagca 240

aaggtagttg accaagctca aaggagagtg ttgaggggag ttgatgacct tgactttttc 300

ataggagatg aagccatcga taaacctaca tatgctacaa agtggccgat acgacatgga 360

atcattgaag actgggatct tatggaaagg ttcatggagc aagtggtttt taaatatctt 420

cgagctgaac ctgaggacca ttatttttta atgacagaac ctccactcaa tacaccagaa 480

aacagagagt atcttgcaga aattatgttt gaatcattta acgtaccagg actctacatt 540

gcagttcagg cagtgctggc cttggcggca tcttggacat ctcgacaagt gggtgaacgt 600

acgttaacgg ggatagtcat tgacagcgga gatggagtca cccatgttat cccagtggca 660

gaaggttatg taattggaag ctgcatcaaa cacatcccga ttgcaggtag agatattacg 720

tatttcattc aacagctgct aagggagagg gaggtgggaa tccctcctga gcagtcactg 780

gagaccgcaa aagccattaa ggagaaatac tgttacattt gccccgatat agtcaaggaa 840

tttgccaagt atgatgtgga tccccggaag tggatcaaac agtacacggg tatcaatgcg 900

atcaaccaga agaagtttgt tatagacgtt ggttacgaaa gattcctggg acctgaaata 960

ttctttcacc cggagtttgc caacccagac tttatggagt ccatctcaga tgttgttgat 1020

gaagtaatac agaactgccc catcgatgtg cggcgcccgc tgtataagcc cgagttcttt 1080

caggtctgcc acaccaagaa ggactatgaa gagtacgggc ccagcatctg ccgccacaac 1140

cccgtctttg gagtcatgtc ctagtgtctg cctgaacgcg tcgttcgatg gtgtcacgtt 1200

ggggaacaag tgtccttcag aacccagaga aggccgccgt tctgtaaata gcgacgtcgg 1260

tgttgctgcc cagcagcgtg cttgcattgc cggtgcatga ggcgcggcgc gggcccttca 1320

gtaaaagcca tttatccgtg tgccgaccgc tgtctgccag cctcctcctt ctcccgccct 1380

cctcaccctc gctctccctc ctcctcctcc tccgagctgc tagctgacaa atacaattct 1440

gaaggaatcc aaatgtgact ttgaaaattg ttagagaaaa caacattaga aaatggcgca 1500

aaatcgttag gtcccaggag agaatgtggg ggcgcaaacc cttttcctcc cagcctattt 1560

ttgtaaataa aatgtttaaa cttgaaatac aaatcgatgt ttatatttcc tatcattttg 1620

tattttatgg tatttggtac aactggctga tactaagcac gaatagatat tgatgttatg 1680

gagtgctgta atccaaagtt tttaattgtg aggcatgttc tgatatgttt ataggcaaac 1740

aaataaaaca gcaaactttt ttgccacatg tttgctagaa aatgattata ctttattgga 1800

gtgacatgaa gtttgaacac taaacagtaa tgtatgagaa ttactacaga tacatgtatc 1860

ttttagtttt ttttgtttga actttctgga gctgttttat agaagatgat ggtttgttgt 1920

cggtgagtgt tggatgaaat acttccttgc accattgtaa taaaagctgt tagaatattt 1980

gtaaatatc 1989

<210> 103

<211> 4786

<212> DNA

<213>Homo sapiens

<400> 103

ctcggcgctg aaattcaaat ttgaacggct gcagaggccg agtccgtcac tggaagccga 60

gaggagagga cagctggttg tgggagagtt cccccgcctc agactcctgg ttttttccag 120

gagacacact gagctgagac tcacttttct cttcctgaat ttgaaccacc gtttccatcg 180

tctcgtagtc cgacgcctgg ggcgatggat ccgtttacgg agaaactgct ggagcgaacc 240

cgtgccaggc gagagaatct tcagagaaaa atggctgaga ggcccacagc agctccaagg 300

tctatgactc atgctaagcg agctagacag ccactttcag aagcaagtaa ccagcagccc 360

ctctctggtg gtgaagagaa atcttgtaca aaaccatcgc catcaaaaaa acgctgttct 420

gacaacactg aagtagaagt ttctaacttg gaaaataaac aaccagttga gtcgacatct 480

gcaaaatctt gttctccaag tcctgtgtct cctcaggtgc agccacaagc agcagatacc 540

atcagtgatt ctgttgctgt cccggcatca ctgctgggca tgaggagagg gctgaactca 600

agattggaag caactgcagc ctcctcagtt aaaacacgta tgcaaaaact tgcagagcaa 660

cggcgccgtt gggataatga tgatatgaca gatgacattc ctgaaagctc actcttctca 720

ccaatgccat cagaggaaaa ggctgcttcc cctcccagac ctctgctttc aaatgcctcg 780

gcaactccag ttggcagaag gggccgtctg gccaatcttg ctgcaactat ttgctcctgg 840

gaagatgatg taaatcactc atttgcaaaa caaaacagtg tacaagaaca gcctggtacc 900

gcttgtttat ccaaattttc ctctgcaagt ggagcatctg ctaggatcaa tagcagcagt 960

gttaagcagg aagctacatt ctgttcccaa agggatggcg atgcctcttt gaataaagcc 1020

ctatcctcaa gtgctgatga tgcgtctttg gttaatgcct caatttccag ctctgtgaaa 1080

gctacttctc cagtgaaatc tactacatct atcactgatg ctaaaagttg tgagggacaa 1140

aatcctgagc tacttccaaa aactcctatt agtcctctga aaacgggggt atcgaaacca 1200

attgtgaagt caactttatc ccagacagtt ccatccaagg gagaattaag tagagaaatt 1260

tgtctgcaat ctcaatctaa agacaaatct acgacaccag gaggaacagg aattaagcct 1320

ttcctggaac gctttggaga gcgttgtcaa gaacatagca aagaaagtcc agctcgtagc 1380

acaccccaca gaacccccat tattactcca aatacaaagg ccatccaaga aagattattc 1440

aagcaagaca catcttcatc tactacccat ttagcacaac agctcaagca ggaacgtcaa 1500

aaagaactag catgtcttcg tggccgattt gacaagggca atatatggag tgcagaaaaa 1560

ggcggaaact caaaaagcaa acaactagaa accaaacagg aaactcactg tcagagcact 1620

cccctcaaaa aacaccaagg tgtttcaaaa actcagtcac ttccagtaac agaaaaggtg 1680

accgaaaacc agataccagc caaaaattct agtacagaac ctaaaggttt cactgaatgc 1740

gaaatgacga aatctagccc tttgaaaata acattgtttt tagaagagga caaatcctta 1800

aaagtaacat cagacccaaa ggttgagcag aaaattgaag tgatacgtga aattgagatg 1860

agtgtggatg atgatgatat caatagttcg aaagtaatta atgacctctt cagtgatgtc 1920

ctagaggaag gtgaactaga tatggagaag agccaagagg agatggatca agcattagca 1980

gaaagcagcg aagaacagga agatgcactg aatatctcct caatgtcttt acttgcacca 2040

ttggcacaaa cagttggtgt ggtaagtcca gagagtttag tgtccacacc tagactggaa 2100

ttgaaagaca ccagcagaag tgatgaaagt ccaaaaccag gaaaattcca aagaactcgt 2160

gtccctcgag ctgaatctgg tgatagcctt ggttctgaag atcgtgatct tctttacagc 2220

attgatgcat atagatctca aagattcaaa gaaacagaac gtccatcaat aaagcaggtg 2280

attgttcgga aggaagatgt tacttcaaaa ctggatgaaa aaaataatgc ctttccttgt 2340

caagttaata tcaaacagaa aatgcaggaa ctcaataacg aaataaatat gcaacagaca 2400

gtgatctatc aagctagcca ggctcttaac tgctgtgttg atgaagaaca tggaaaaggg 2460

tccctagaag aagctgaagc agaaagactt cttctaattg caactgggaa gagaacactt 2520

ttgattgatg aattgaataa attgaagaac gaaggacctc agaggaagaa taaggctagt 2580

ccccaaagtg aatttatgcc atccaaagga tcagttactt tgtcagaaat ccgcttgcct 2640

ctaaaagcag attttgtctg cagtacggtt cagaaaccag atgcagcaaa ttactattac 2700

ttaattatac taaaagcagg agctgaaaat atggtagcca caccattagc aagtacttca 2760

aactctctta acggtgatgc tctgacattc actactacat ttactctgca agatgtatcc 2820

aatgactttg aaataaatat tgaagtttac agcttggtgc aaaagaaaga tccctcaggc 2880

cttgataaga agaaaaaaac atccaagtcc aaggctatta ctccaaagcg actcctcaca 2940

tctataacca caaaaagcaa cattcattct tcagtcatgg ccagtccagg aggtcttagt 3000

gctgtgcgaa ccagcaactt cgcccttgtt ggatcttaca cattatcatt gtcttcagta 3060

ggaaatacta agtttgttct ggacaaggtc ccctttttat cttctttgga aggtcatatt 3120

tatttaaaaa taaaatgtca agtgaattcc agtgttgaag aaagaggttt tctaaccata 3180

tttgaagatg ttagtggttt tggtgcctgg catcgaagat ggtgtgttct ttctggaaac 3240

tgtatatctt attggactta tccagatgat gagaaacgca agaatcccat aggaaggata 3300

aatctggcta attgtaccag tcgtcagata gaaccagcca acagagaatt ttgtgcaaga 3360

cgcaacactt ttgaattaat tactgtccga ccacaaagag aagatgaccg agagactctt 3420

gtcagccaat gcagggacac actctgtgtt accaagaact ggctgtctgc agatactaaa 3480

gaagagcggg atctctggat gcaaaaactc aatcaagttc ttgttgatat tcgcctctgg 3540

caacctgatg cttgctacaa acctattgga aagccttaaa ccgggaaatt tccatgctat 3600

ctagaggttt ttgatgtcat cttaagaaac acacttaaga gcatcagatt tactgattgc 3660

attttatgct ttaagtacga aagggtttgt gccaatattc actacgtatt atgcagtatt 3720

tatatctttt gtatgtaaaa ctttaactga tttctgtcat tcatcaatga gtagaagtaa 3780

atacattata gttgattttg ctaaatctta atttaaaagc ctcattttcc tagaaatcta 3840

attattcagt tattcatgac aatatttttt taaaagtaag aaattctgag ttgtcttctt 3900

ggagctgtag gtcttgaagc agcaacgtct ttcaggggtt ggagacagaa acccattctc 3960

caatctcagt agttttttcg aaaggctgtg atcatttatt gatcgtgata tgacttgtta 4020

ctagggtact gaaaaaaatg tctaaggcct ttacagaaac atttttagta atgaggatga 4080

gaactttttc aaatagcaaa tatatattgg cttaaagcat gaggctgtct tcagaaaagt 4140

gatgtggaca taggaggcaa tgtgtgagac ttgggggttc aatattttat atagaagagt 4200

taataagcac atggtttaca tttactcagc tactatatat gcagtgtggt gcacattttc 4260

acagaattct ggcttcatta agatcattat ttttgctgcg tagcttacag acttagcata 4320

ttagtttttt ctactcctac aagtgtaaat tgaaaaatct ttatattaaa aaagtaaact 4380

gttatgaagc tgctatgtac taataatact ttgcttgcca aagtgtttgg gttttgttgt 4440

tgtttgtttg tttgtttgtt tttggttcat gaacaacagt gtctagaaac ccattttgaa 4500

agtggaaaat tattaagtca cctatcacct ttaaacgcct ttttttaaaa ttataaaata 4560

ttgtaaagca gggtctcaac ttttaaatac actttgaact tcttctctga attattaaag 4620

ttctttatga cctcatttat aaacactaaa ttctgtcacc tcctgtcatt ttatttttta 4680

ttcattcaaa tgtatttttt cttgtgcata ttataaaaat atattttatg agctcttact 4740

caaataaata cctgtaaatg tctaaaggaa aaaaaaaaaa aaaaaa 4786

<210> 104

<211> 3885

<212> DNA

<213>Homo sapiens

<400> 104

aggccggggc ggggctggga agtagtcggg cggggttgtg agacgccgcg ctcagcttcc 60

atcgctgggc ggtcaacaag tgcgggcctg gctcagcgcg ggggggcgcg gagaccgcga 120

ggcgaccggg agcggctggg ttcccggctg cgcgcccttc ggccaggccg ggagccgcgc 180

cagtcggagc ccccggccca gcgtggtccg cctccctctc ggcgtccacc tgcccggagt 240

actgccagcg ggcatgaccg acccaccagg ggcgccgccg ccggcgctcg caggccgcgg 300

atgaagaaga aaacccggcg ccgctcgacc cggagcgagg agttgacccg gagcgaggag 360

ttgaccctga gtgaggaagc gacctggagt gaagaggcga cccagagtga ggaggcgacc 420

cagggcgaag agatgaatcg gagccaggag gtgacccggg acgaggagtc gacccggagc 480

gaggaggtga ccagggagga aatggcggca gctgggctca ccgtgactgt cacccacagc 540

aatgagaagc acgaccttca tgttacctcc cagcagggca gcagtgaacc agttgtccaa 600

gacctggccc aggttgttga agaggtcata ggggttccac agtcttttca gaaactcata 660

tttaagggaa aatctctgaa ggaaatggaa acaccgttgt cagcacttgg aatacaagat 720

ggttgccggg tcatgttaat tgggaaaaag aacagtccac aggaagaggt tgaactaaag 780

aagttgaaac atttggagaa gtctgtggag aagatagctg accagctgga agagttgaat 840

aaagagctta ctggaatcca gcagggtttt ctgcccaagg atttgcaagc tgaagctctc 900

tgcaaacttg ataggagagt aaaagccaca atagagcagt ttatgaagat cttggaggag 960

attgacacac tgatcctgcc agaaaatttc aaagacagta gattgaaaag gaaaggcttg 1020

gtaaaaaagg ttcaggcatt cctagccgag tgtgacacag tggagcagaa catctgccag 1080

gagactgagc ggctgcagtc tacaaacttt gccctggccg agtgaggtgt agcagaaaaa 1140

ggctgtgctg ccctgaagaa tggcgccacc agctctgccg tctctggagc ggaatttacc 1200

tgatttcttc agggctgctg ggggcaactg gccatttgcc aattttccta ctctcacact 1260

ggttctcaat gaaaaatagt gtctttgtga ttttgagtaa agctcctatc tgttttctcc 1320

ttctgtctct gtggttgtac tgtccagcaa tccacctttt ctggagaggg ccacctctgc 1380

ccaaattttc ccagctgttt ggacctctgg gtgctttctt tgggctggtg agagctctaa 1440

tttgccttgg gccagtttca ggtttatagg ccccctcagt cttcagatac atgagggctt 1500

ctttgctctt gtgatcgtgt agtcccatag ctgtaaaacc agaatcacca ggaggttgca 1560

cctagtcagg aatattggga atggcctaga acaaggtgtt tggcacataa gtagaccact 1620

tatccctcat tgtgacctaa ttccagagca tctggctggg ttgttgggtt ctagactttg 1680

tcctcacctc ccagtgaccc tgactagcca caggccatga gataccaggg ggccgttcct 1740

tggatggagc ctgtggttga tgcaaggctt ccttgtcccc aagcaagtct tcagaaggtt 1800

agaacccagt gttgactgag tctgtgcttg aaaccaggcc agagccatgg attaggaagg 1860

gcaaagagaa ggcaccagaa tgagtaaagc aggcaggtgg tgaagccaac cataaacttc 1920

tcaggagtga catgtgcttc cttcaaaggc atttttgtta accatatcct tctgagttct 1980

atgtttcctt cacagctgtt ctatccattt tgtggactgt cccccacccc caccccatca 2040

ttgtttttaa aaaattaagg cctggcgcag cagctcatgc ctataatccc agcactttgg 2100

gaggctgagg cgggcggatc acttgaggcc aggagtttga gaccagccca ggcaacatag 2160

caaaacccca ttctgcttta aaaaaaaaaa aaaaaaaaat tagcttggcg tagtggcatg 2220

tgcctataat cccagctact ggggaggctg aggcacaaga atcatttgaa cctgggaggt 2280

agaggttgct gtgagccgag attacgcccc tgcactccag cctgggtcac agagtgagac 2340

tccatctcag aaaaaaaaaa aattgagtca ggtgcagtag ctccttcctg tagtcccagc 2400

tacttgggag gctgaggcta gaggatcact tgagcccagg agtttgagtc tagtctgggc 2460

aacatagcaa gaccccatct ctaaaattta agtaagtaaa agtagataaa taaaaagaaa 2520

aaaaaactgt ttatgtgctc atcataaagt agaagagtgg tttgcttttt tttttttttt 2580

tggattaatg aggaaatcat tctgtggctc tagtcataat ttatgcttaa taacattgat 2640

agtagccctt tgcgctataa ctctacctaa agactcacat catttggcag agagagagtc 2700

gttgaagtcc caggaattca ggactgggca ggttaagacc tcagacaagg tagtagaggt 2760

agacttgtgg acaaggctcg ggtcccagcc caccgcaccc caactttaat cagagtggtt 2820

cactattgat ctatttttgt gtgatagctg tgtggcgtgg gccacaacat ttaatgagaa 2880

gttactgtgc accaaactgc cgaacaccat tctaaactat tcatatatat tagtcattta 2940

attcttacat aacttgagag gtagacagat atccttattt tagagatgag gaaaccaaga 3000

gaacttaggt cattagcgca aggttgtaga gtaagcggca aagccaagac acaaagctgg 3060

gtggtttggt ttcagagcca gtgcttttcc cctctactgt actgcctctc aaccaacaca 3120

gggttgcaca ggcccattct ctgatttttt tcctcttgtc ctctgcctct ccctctagct 3180

cccacttcct ctctgctcta gttcattttc tttagagcag cccgagtgat catgaagtgc 3240

aaatcttgcc atgtcagtcc cctgcttaga accctccaat ggctcacttt ctctttaggc 3300

aaaagtcttt accccatgcc ttctcccatc tcatctcaac cccctcattt gttggctgtc 3360

tgctgtcagc cactcttctt tcaggtcctc agatgcactg caccctctcc tgcctggggg 3420

tctttgctcc tgctactacc tctgcttgaa cagctcctca ccttccttcc tccaacccta 3480

cccttgtata ggtgactttt gttcatcctt cagaattcaa ctcacatgtc tcttgcatgg 3540

agaaccctca cctactgtgt tgagaccctg tccagccccc aggtgggatc ctctctcgac 3600

ttcccataca tttctttcac agcatttaca tagtccatga tagtttactt gtgggattat 3660

ttggttaatc tttgccttta acaccagggt tccttgggtg aaggagcttc tttatcttgg 3720

taacagcatt atttcaagca taacttgtaa tatagttata ttacatatat aacatatata 3780

tatataacat aacatatata acatatataa caagcataac ttgttatata gtcttgtata 3840

tagtaagacc tcaataaata tttggagaac aaaaaaaaaa aaaaa 3885

<210> 105

<211> 6492

<212> DNA

<213>Homo sapiens

<400> 105

tttctgtgaa gcagaagtct gggaatcgat ctggaaatcc tcctaatttt tactccctct 60

ccccgcgact cctgattcat tgggaagttt caaatcagct ataactggag agtgctgaag 120

attgatggga tcgttgcctt atgcatttgt tttggtttta caaaaaggaa acttgacaga 180

ggatcatgct gtacttaaaa aatacaacat cacagaggaa gtagactgat attaacaata 240

cttactaata ataacgtgcc tcatgaaata aagatccgaa aggaattgga ataaaaattt 300

cctgcatctc atgccaaggg ggaaacacca gaatcaagtg ttccgcgtga ttgaagacac 360

cccctcgtcc aagaatgcaa agcacatcca ataaaatagc tggattataa ctcctcttct 420

ttctctgggg gccgtggggt gggagctggg gcgagaggtg ccgttggccc ccgttgcttt 480

tcctctggga aggatggcgc acgctgggag aacagggtac gataaccggg agatagtgat 540

gaagtacatc cattataagc tgtcgcagag gggctacgag tgggatgcgg gagatgtggg 600

cgccgcgccc ccgggggccg cccccgcacc gggcatcttc tcctcccagc ccgggcacac 660

gccccatcca gccgcatccc gggacccggt cgccaggacc tcgccgctgc agaccccggc 720

tgcccccggc gccgccgcgg ggcctgcgct cagcccggtg ccacctgtgg tccacctgac 780

cctccgccag gccggcgacg acttctcccg ccgctaccgc cgcgacttcg ccgagatgtc 840

cagccagctg cacctgacgc ccttcaccgc gcggggacgc tttgccacgg tggtggagga 900

gctcttcagg gacggggtga actgggggag gattgtggcc ttctttgagt tcggtggggt 960

catgtgtgtg gagagcgtca accgggagat gtcgcccctg gtggacaaca tcgccctgtg 1020

gatgactgag tacctgaacc ggcacctgca cacctggatc caggataacg gaggctggga 1080

tgcctttgtg gaactgtacg gccccagcat gcggcctctg tttgatttct cctggctgtc 1140

tctgaagact ctgctcagtt tggccctggt gggagcttgc atcaccctgg gtgcctatct 1200

gggccacaag tgaagtcaac atgcctgccc caaacaaata tgcaaaaggt tcactaaagc 1260

agtagaaata atatgcattg tcagtgatgt accatgaaac aaagctgcag gctgtttaag 1320

aaaaaataac acacatataa acatcacaca cacagacaga cacacacaca cacaacaatt 1380

aacagtcttc aggcaaaacg tcgaatcagc tatttactgc caaagggaaa tatcatttat 1440

tttttacatt attaagaaaa aaagatttat ttatttaaga cagtcccatc aaaactcctg 1500

tctttggaaa tccgaccact aattgccaag caccgcttcg tgtggctcca cctggatgtt 1560

ctgtgcctgt aaacatagat tcgctttcca tgttgttggc cggatcacca tctgaagagc 1620

agacggatgg aaaaaggacc tgatcattgg ggaagctggc tttctggctg ctggaggctg 1680

gggagaaggt gttcattcac ttgcatttct ttgccctggg ggctgtgata ttaacagagg 1740

gagggttcct gtggggggaa gtccatgcct ccctggcctg aagaagagac tctttgcata 1800

tgactcacat gatgcatacc tggtgggagg aaaagagttg ggaacttcag atggacctag 1860

tacccactga gatttccacg ccgaaggaca gcgatgggaa aaatgccctt aaatcatagg 1920

aaagtatttt tttaagctac caattgtgcc gagaaaagca ttttagcaat ttatacaata 1980

tcatccagta ccttaagccc tgattgtgta tattcatata ttttggatac gcacccccca 2040

actcccaata ctggctctgt ctgagtaaga aacagaatcc tctggaactt gaggaagtga 2100

acatttcggt gacttccgca tcaggaaggc tagagttacc cagagcatca ggccgccaca 2160

agtgcctgct tttaggagac cgaagtccgc agaacctgcc tgtgtcccag cttggaggcc 2220

tggtcctgga actgagccgg ggccctcact ggcctcctcc agggatgatc aacagggcag 2280

tgtggtctcc gaatgtctgg aagctgatgg agctcagaat tccactgtca agaaagagca 2340

gtagaggggt gtggctgggc ctgtcaccct ggggccctcc aggtaggccc gttttcacgt 2400

ggagcatggg agccacgacc cttcttaaga catgtatcac tgtagaggga aggaacagag 2460

gccctgggcc cttcctatca gaaggacatg gtgaaggctg ggaacgtgag gagaggcaat 2520

ggccacggcc cattttggct gtagcacatg gcacgttggc tgtgtggcct tggcccacct 2580

gtgagtttaa agcaaggctt taaatgactt tggagagggt cacaaatcct aaaagaagca 2640

ttgaagtgag gtgtcatgga ttaattgacc cctgtctatg gaattacatg taaaacatta 2700

tcttgtcact gtagtttggt tttatttgaa aacctgacaa aaaaaaagtt ccaggtgtgg 2760

aatatggggg ttatctgtac atcctggggc attaaaaaaa aaatcaatgg tggggaacta 2820

taaagaagta acaaaagaag tgacatcttc agcaaataaa ctaggaaatt tttttttctt 2880

ccagtttaga atcagccttg aaacattgat ggaataactc tgtggcatta ttgcattata 2940

taccatttat ctgtattaac tttggaatgt actctgttca atgtttaatg ctgtggttga 3000

tatttcgaaa gctgctttaa aaaaatacat gcatctcagc gtttttttgt ttttaattgt 3060

atttagttat ggcctataca ctatttgtga gcaaaggtga tcgttttctg tttgagattt 3120

ttatctcttg attcttcaaa agcattctga gaaggtgaga taagccctga gtctcagcta 3180

cctaagaaaa acctggatgt cactggccac tgaggagctt tgtttcaacc aagtcatgtg 3240

catttccacg tcaacagaat tgtttattgt gacagttata tctgttgtcc ctttgacctt 3300

gtttcttgaa ggtttcctcg tccctgggca attccgcatt taattcatgg tattcaggat 3360

tacatgcatg tttggttaaa cccatgagat tcattcagtt aaaaatccag atggcaaatg 3420

accagcagat tcaaatctat ggtggtttga cctttagaga gttgctttac gtggcctgtt 3480

tcaacacaga cccacccaga gccctcctgc cctccttccg cgggggcttt ctcatggctg 3540

tccttcaggg tcttcctgaa atgcagtggt gcttacgctc caccaagaaa gcaggaaacc 3600

tgtggtatga agccagacct ccccggcggg cctcagggaa cagaatgatc agacctttga 3660

atgattctaa tttttaagca aaatattatt ttatgaaagg tttacattgt caaagtgatg 3720

aatatggaat atccaatcct gtgctgctat cctgccaaaa tcattttaat ggagtcagtt 3780

tgcagtatgc tccacgtggt aagatcctcc aagctgcttt agaagtaaca atgaagaacg 3840

tggacgtttt taatataaag cctgttttgt cttttgttgt tgttcaaacg ggattcacag 3900

agtatttgaa aaatgtatat atattaagag gtcacggggg ctaattgctg gctggctgcc 3960

ttttgctgtg gggttttgtt acctggtttt aataacagta aatgtgccca gcctcttggc 4020

cccagaactg tacagtattg tggctgcact tgctctaaga gtagttgatg ttgcattttc 4080

cttattgtta aaaacatgtt agaagcaatg aatgtatata aaagcctcaa ctagtcattt 4140

ttttctcctc ttcttttttt tcattatatc taattatttt gcagttgggc aacagagaac 4200

catccctatt ttgtattgaa gagggattca catctgcatc ttaactgctc tttatgaatg 4260

aaaaaacagt cctctgtatg tactcctctt tacactggcc agggtcagag ttaaatagag 4320

tatatgcact ttccaaattg gggacaaggg ctctaaaaaa agccccaaaa ggagaagaac 4380

atctgagaac ctcctcggcc ctcccagtcc ctcgctgcac aaatactccg caagagaggc 4440

cagaatgaca gctgacaggg tctatggcca tcgggtcgtc tccgaagatt tggcaggggc 4500

agaaaactct ggcaggctta agatttggaa taaagtcaca gaattaagga agcacctcaa 4560

tttagttcaa acaagacgcc aacattctct ccacagctca cttacctctc tgtgttcaga 4620

tgtggccttc catttatatg tgatctttgt tttattagta aatgcttatc atctaaagat 4680

gtagctctgg cccagtggga aaaattagga agtgattata aatcgagagg agttataata 4740

atcaagatta aatgtaaata atcagggcaa tcccaacaca tgtctagctt tcacctccag 4800

gatctattga gtgaacagaa ttgcaaatag tctctatttg taattgaact tatcctaaaa 4860

caaatagttt ataaatgtga acttaaactc taattaattc caactgtact tttaaggcag 4920

tggctgtttt tagactttct tatcacttat agttagtaat gtacacctac tctatcagag 4980

aaaaacagga aaggctcgaa atacaagcca ttctaaggaa attagggagt cagttgaaat 5040

tctattctga tcttattctg tggtgtcttt tgcagcccag acaaatgtgg ttacacactt 5100

tttaagaaat acaattctac attgtcaagc ttatgaaggt tccaatcaga tctttattgt 5160

tattcaattt ggatctttca gggatttttt ttttaaatta ttatgggaca aaggacattt 5220

gttggagggg tgggagggag gaagaatttt taaatgtaaa acattcccaa gtttggatca 5280

gggagttgga agttttcaga ataaccagaa ctaagggtat gaaggacctg tattggggtc 5340

gatgtgatgc ctctgcgaag aaccttgtgt gacaaatgag aaacattttg aagtttgtgg 5400

tacgaccttt agattccaga gacatcagca tggctcaaag tgcagctccg tttggcagtg 5460

caatggtata aatttcaagc tggatatgtc taatgggtat ttaaacaata aatgtgcagt 5520

tttaactaac aggatattta atgacaacct tctggttggt agggacatct gtttctaaat 5580

gtttattatg tacaatacag aaaaaaattt tataaaatta agcaatgtga aactgaattg 5640

gagagtgata atacaagtcc tttagtctta cccagtgaat cattctgttc catgtctttg 5700

gacaaccatg accttggaca atcatgaaat atgcatctca ctggatgcaa agaaaatcag 5760

atggagcatg aatggtactg taccggttca tctggactgc cccagaaaaa taacttcaag 5820

caaacatcct atcaacaaca aggttgttct gcataccaag ctgagcacag aagatgggaa 5880

cactggtgga ggatggaaag gctcgctcaa tcaagaaaat tctgagacta ttaataaata 5940

agactgtagt gtagatactg agtaaatcca tgcacctaaa ccttttggaa aatctgccgt 6000

gggccctcca gatagctcat ttcattaagt ttttccctcc aaggtagaat ttgcaagagt 6060

gacagtggat tgcatttctt ttggggaagc tttcttttgg tggttttgtt tattatacct 6120

tcttaagttt tcaaccaagg tttgcttttg ttttgagtta ctggggttat ttttgtttta 6180

aataaaaata agtgtacaat aagtgttttt gtattgaaag cttttgttat caagattttc 6240

atacttttac cttccatggc tctttttaag attgatactt ttaagaggtg gctgatattc 6300

tgcaacactg tacacataaa aaatacggta aggatacttt acatggttaa ggtaaagtaa 6360

gtctccagtt ggccaccatt agctataatg gcactttgtt tgtgttgttg gaaaaagtca 6420

cattgccatt aaactttcct tgtctgtcta gttaatattg tgaagaaaaa taaagtacag 6480

tgtgagatac tg 6492

<210> 106

<211> 2724

<212> DNA

<213>Homo sapiens

<400> 106

cccagaaggc cgcggggggt ggaccgccta agagggcgtg cgctcccgac atgccccgcg 60

gcgcgccatt aaccgccaga tttgaatcgc gggacccgtt ggcagaggtg gcggcggcgg 120

catgggtgcc ccgacgttgc cccctgcctg gcagcccttt ctcaaggacc accgcatctc 180

tacattcaag aactggccct tcttggaggg ctgcgcctgc accccggagc ggatggccga 240

ggctggcttc atccactgcc ccactgagaa cgagccagac ttggcccagt gtttcttctg 300

cttcaaggag ctggaaggct gggagccaga tgacgacccc attgggccgg gcacggtggc 360

ttacgcctgt aataccagca ctttgggagg ccgaggcggg cggatcacga gagaggaaca 420

taaaaagcat tcgtccggtt gcgctttcct ttctgtcaag aagcagtttg aagaattaac 480

ccttggtgaa tttttgaaac tggacagaga aagagccaag aacaaaattg caaaggaaac 540

caacaataag aagaaagaat ttgaggaaac tgcggagaaa gtgcgccgtg ccatcgagca 600

gctggctgcc atggattgag gcctctggcc ggagctgcct ggtcccagag tggctgcacc 660

acttccaggg tttattccct ggtgccacca gccttcctgt gggcccctta gcaatgtctt 720

aggaaaggag atcaacattt tcaaattaga tgtttcaact gtgctcttgt tttgtcttga 780

aagtggcacc agaggtgctt ctgcctgtgc agcgggtgct gctggtaaca gtggctgctt 840

ctctctctct ctctcttttt tgggggctca tttttgctgt tttgattccc gggcttacca 900

ggtgagaagt gagggaggaa gaaggcagtg tcccttttgc tagagctgac agctttgttc 960

gcgtgggcag agccttccac agtgaatgtg tctggacctc atgttgttga ggctgtcaca 1020

gtcctgagtg tggacttggc aggtgcctgt tgaatctgag ctgcaggttc cttatctgtc 1080

acacctgtgc ctcctcagag gacagttttt ttgttgttgt gtttttttgt tttttttttt 1140

ttggtagatg catgacttgt gtgtgatgag agaatggaga cagagtccct ggctcctcta 1200

ctgtttaaca acatggcttt cttattttgt ttgaattgtt aattcacaga atagcacaaa 1260

ctacaattaa aactaagcac aaagccattc taagtcattg gggaaacggg gtgaacttca 1320

ggtggatgag gagacagaat agagtgatag gaagcgtctg gcagatactc cttttgccac 1380

tgctgtgtga ttagacaggc ccagtgagcc gcggggcaca tgctggccgc tcctccctca 1440

gaaaaaggca gtggcctaaa tcctttttaa atgacttggc tcgatgctgt gggggactgg 1500

ctgggctgct gcaggccgtg tgtctgtcag cccaaccttc acatctgtca cgttctccac 1560

acgggggaga gacgcagtcc gcccaggtcc ccgctttctt tggaggcagc agctcccgca 1620

gggctgaagt ctggcgtaag atgatggatt tgattcgccc tcctccctgt catagagctg 1680

cagggtggat tgttacagct tcgctggaaa cctctggagg tcatctcggc tgttcctgag 1740

aaataaaaag cctgtcattt caaacactgc tgtggaccct actgggtttt taaaatattg 1800

tcagtttttc atcgtcgtcc ctagcctgcc aacagccatc tgcccagaca gccgcagtga 1860

ggatgagcgt cctggcagag acgcagttgt ctctgggcgc ttgccagagc cacgaacccc 1920

agacctgttt gtatcatccg ggctccttcc gggcagaaac aactgaaaat gcacttcaga 1980

cccacttatt tctgccacat ctgagtcggc ctgagataga cttttccctc taaactggga 2040

gaatatcaca gtggtttttg ttagcagaaa atgcactcca gcctctgtac tcatctaagc 2100

tgcttatttt tgatatttgt gtcagtctgt aaatggatac ttcactttaa taactgttgc 2160

ttagtaattg gctttgtaga gaagctggaa aaaaatggtt ttgtcttcaa ctcctttgca 2220

tgccaggcgg tgatgtggat ctcggcttct gtgagcctgt gctgtgggca gggctgagct 2280

ggagccgccc ctctcagccc gcctgccacg gcctttcctt aaaggccatc cttaaaacca 2340

gaccctcatg gctaccagca cctgaaagct tcctcgacat ctgttaataa agccgtaggc 2400

ccttgtctaa gtgcaaccgc ctagactttc tttcagatac atgtccacat gtccattttt 2460

caggttctct aagttggagt ggagtctggg aagggttgtg aatgaggctt ctgggctatg 2520

ggtgaggttc caatggcagg ttagagcccc tcgggccaac tgccatcctg gaaagtagag 2580

acagcagtgc ccgctgccca gaagagacca gcaagccaaa ctggagcccc cattgcaggc 2640

tgtcgccatg tggaaagagt aactcacaat tgccaataaa gtctcatgtg gttttatcta 2700

aaaaaaaaaa aaaaaaaaaa aaaa 2724

<210> 107

<211> 4934

<212> DNA

<213>Homo sapiens

<400> 107

aatgagggta tttataaact acttaaatta taaaaagaat gagacatcag acttacagtt 60

ttggatacta atttttttca cttaacgttc attatgtgat aggagttttc catcctatta 120

taccgctgtg cgatctgatc ttgggcacgt taaccaacct cttgttgcct cgattttctc 180

acctgtaaaa gtgggggtaa tcataatgct tacttagtag gatagccctg aagaataagt 240

gacttagcga acataaatag cttacaatag ggttttcagc atgggaagga ttcagtaaat 300

gttagctgtc atcatcacca cctacaaagg aagcaatact gtgctgaaag tttttccatc 360

attaatgtaa tttctatagt acgattccca agaagatatt aaaattatgg aaataaaggt 420

attggtatat tcctaattat ttcctaaaag attgtattga taaatatgct catccttccc 480

ttaacgggat gcattccaga aaaacaagtc aaatgttaga caaagtatca gaagggaaat 540

tctgtagcca gagagctaaa aattacaata gggtctctaa ttatacttca acttttttag 600

gaataattct cagtgtgttt tcccacattt catatgtaat tttttttttt tttttttttt 660

gagacagagc ctcgccctgt caccaggctg gagtacagtg gcgcgatctc ggctcactgc 720

aacttccacc tgctgggttc aagcaattct tctgacctca ggtgatccac ccgcctcggc 780

ctcccaaagt gctgggatta taacaggcgt ggcatgagtc accgcgcccg gccgatcttt 840

acttttttat tctttgtacc ccctgcctat ccagttagca tgtgattaaa gtcaaagatt 900

tgccactttg ggccacatct attaattttc atctttgtta taattgtatt tagtttttga 960

tctacactgc ttattactcc cagtcatttt ttatagaact gaaaatctgg taaaatactc 1020

aaaattgcac tgacttctat gtagaggcga cactccatca gaaccgtggg ctgacaggga 1080

atcccactgt gcaggagctg cgcgcatttt catttctgat tctctttggc gtatccagga 1140

ctctgatgac atgatcatat atttatcagt agtaacaggt tgggccattt gttttttgtg 1200

gtaaatcata tatttaagat tttagaaata agttgatagc catgtatttt ggaatttgaa 1260

aaagacattg cattactcag cttcaaatta agctttaatc aaatagtgaa actttccatt 1320

aatggacagt gtataccttt ttgtgtattt aaaaaaaaaa acactgaata tagtgccttt 1380

gtgacagggg agcttggttc ctgacaatgt cctcttgagc cttttttttt tttttgagat 1440

ggagtctcac tgtgtcaccc aggctggagt gcagtggcgc catcttggct cactgcaacc 1500

tccgccccct gggttcaagt gattctcatt cctcagcttc ctaagtagct gggattacag 1560

gcacgcacca ccatgaccag ctaattttta tacttttagt agagacaggg ttttgccatg 1620

ttggctaggt tggtctcgaa ctcctgacct caagtaatcc acccaccatg gcctccccaa 1680

agtgctggga ttacaggcgt gagccatttc acccggcctc tcttccgtct ttgagctgtg 1740

aggaaatagc tacattacat gagctgctag atctgcctta tggtcagaaa tgaaggttga 1800

actctcagga acagtgacat atatacacac tgatatttcc aaagtacaat gccccaaatt 1860

gatccacaaa ggaattaagg tcatttgcaa caaaatcaca gaatagtaac aaataaatag 1920

aagataaata tggccaggga tgctgcaaac tgatatactg ccaagtttat cagttgggaa 1980

tcccaacagt gaaaagcata aaaatgaaag gaattttaag gagacttttt atagaagagt 2040

gggaaggatt ggaggagcca acaagtgatg gtgaggcaca cagggaagag cttcagtggg 2100

caccatcccc tctctggttt gaaggggtag ggaggggacc agagctggga ggagggggct 2160

ggaatactgc tggaggagcc actcccttcc agacctgctg tggccatcac agaatgcagc 2220

cactgccaga gcagcagccc gaggaaccag gcagggggag cacaagtacc ctagcctctc 2280

tctttctgtt tcttgcctgc cgatctcctc cactggctaa acccagctgg atgctaagag 2340

tacagtcagc ctgcctgctg aggagggacc accagggacc accatcagca agggatccaa 2400

tgtctttctg cctctgcaga atgaaggttg gggcgcgggg ggcgctctac ttcttaggga 2460

tattgtggga ataaaaggaa ataggcaaaa aatgtttttg aaaaacaaag cacatactgc 2520

gcacccgtgg gccactactg cttttgaccc ctggctctgt ttcatgaagt aatgtcgtgt 2580

cattctcttt ttaggtgcta caggatttct ttaggtttgt tttctgtcca ccatatttca 2640

actcatgtgt gctgtttgtt gtgctaaaac aaatatttgc tgatgcctga gtgaatagtt 2700

gaatatttta tataagtcaa atttatacgt aatgattttt cttgtaactt agccgtttct 2760

cttttacaaa ctcagaaaac ctcagacttt gaaaaggcct tgaagttcct cacctgaaat 2820

ctgagaactt ggagcgcctt aaaaaatcta aaggaaaaca aaacagtgaa agaacatgat 2880

atagtcagtg tagagaataa aattatttat gtaattaata ttgaggatgc agataacaca 2940

ttgtgaaatc ttgcttgtaa aaaatctcga tctgctgaag aaagatgttc tctctagaga 3000

tctttgaaag cataattatt gagcttttaa aatgttagaa acaaaagtta gacccacaca 3060

tattctggcg tgtggaagat ttgcattcct tcccctgccc gccccgcccc cacacttgtg 3120

agttgtgcct gtgtacgcag ttcctgtagc actcggctgg gcagaaatca tctttcagca 3180

ctaagggaac atagttatga tctggacctt ctgggagtgg tcagtgccca agaacaggta 3240

tgggactcca gaaagttctg ctctcaaccc tattttgaaa tagagttaca cattgttcta 3300

caattatttg agttaataag cagctctttt caaacgtgat tatgcccttc caagtttaaa 3360

tacactagac tttagtgaaa gtaattgacc tcatctcatt tctctcctgt tatattaaga 3420

tcactttcag taaaaggtag aagcttttga agtggtgagg aggaggtaga ggagggacat 3480

agagcagata ggggctggaa agtggggtga ggaagagagt ggcttctctt tggcagagta 3540

ccaaggaaaa gccctatctg tacagaacct ttgtgcctgg gaacttgatg gctgcaacct 3600

gagcctcaac ctagtttgct tgcggagcca gaagagaagc taaaaacctt cagttaacca 3660

agccagacac caagaaagtt aaaccgaaag agaacccccc accccccgca aaaaaaagaa 3720

gtaaagtggg ttaaagtgat atcatgttag cacagaaaga gaacataagg gtcatctaag 3780

ttcatctgcc ccctcttcta tttcaaggtg cagaaactaa ggcacaaggg accccgtgtc 3840

ctgctcttga tcacatagct agtgggtgcc aagccaggtc tagaactctg ttctctgggg 3900

tcacaggctg gctcttcatc cctctagaga gatagctcat ctgtgtgcac ctgagcccgt 3960

tgtgtttcgg agtcaaagca aataaaggct caaactccaa gactgttttg cagaccggct 4020

gcagtagata tggggggagg agaaacctgc tttaaattgc ttcaagcaag ttgtttctgc 4080

aaaggtgttg acttttttct ttcaactttc tagtgagtca ctgcagcctg agctgttatt 4140

tgtcattatg caataattca ggaactaact caagattctt ctttttaaat tatttgttta 4200

tttagagaca gagtcttgct ctgttgccca ggctggagtg cagtggtgtg atctcggctc 4260

actgcagcct ctgcctcctg ggttcaagca attctcatgt ctcagcctcc cgaatagctg 4320

gtattgcagg ctcgtgccac caccccctgc taatttttgt aattttagtg gagacacggt 4380

ttcgccatgt tggccgggct cgtcttgagc tcctggcctc aggtgatccg cccgcctcgg 4440

cctcccaaag tgctgggatt gcagccgtga gcctccacac ccggcctatt tatttatttt 4500

taaattggct gctcttagaa aggcatacca tgtttctgga tgggaaggct tattaattca 4560

ccctaattta atgtataaat ttgatgcaat catagtcaca gtcccagtgg aattttttaa 4620

cttggtaaga tgttctaaaa ttaatgagag aacttgaatt accaggtatt gaaacactgt 4680

aaagccacaa tcatgtaaac agtatgttat aaccatggga atagaggtct gtgatacagc 4740

agaaaaaagt gaaaaaaaga ataactgtat tcataaaaat ttaaatgtgg agtcactggg 4800

ggaaaggatt aaatattcga taatgtagaa acaactcaac tatttggaga aatgtaaatt 4860

tagagcctta tctcatgcca tataccaaaa tactatttag atttgattaa aaaataaaaa 4920

aaaaaaaaaa aaaa 4934

<210> 108

<211> 2177

<212> DNA

<213>Homo sapiens

<400> 108

cgaacgcctt cgcgcgatcg ccctggaaac gcattctctg cgaccggcag ccgccaatgg 60

gaagggagtg agtgccacga acaggccaat aaggagggag cagtgcgggg tttaaatctg 120

aggctaggct ggctcttctc ggcgtgctgc ggcggaacgg ctgttggttt ctgctgggtg 180

taggtccttg gctggtcggg cctccggtgt tctgcttctc cccgctgagc tgctgcctgg 240

tgaagaggaa gccatggcgc tccgagtcac caggaactcg aaaattaatg ctgaaaataa 300

ggcgaagatc aacatggcag gcgcaaagcg cgttcctacg gcccctgctg caacctccaa 360

gcccggactg aggccaagaa cagctcttgg ggacattggt aacaaagtca gtgaacaact 420

gcaggccaaa atgcctatga agaaggaagc aaaaccttca gctactggaa aagtcattga 480

taaaaaacta ccaaaacctc ttgaaaaggt acctatgctg gtgccagtgc cagtgtctga 540

gccagtgcca gagccagaac ctgagccaga acctgagcct gttaaagaag aaaaactttc 600

gcctgagcct attttggttg atactgcctc tccaagccca atggaaacat ctggatgtgc 660

ccctgcagaa gaagacctgt gtcaggcttt ctctgatgta attcttgcag taaatgatgt 720

ggatgcagaa gatggagctg atccaaacct ttgtagtgaa tatgtgaaag atatttatgc 780

ttatctgaga caacttgagg aagagcaagc agtcagacca aaatacctac tgggtcggga 840

agtcactgga aacatgagag ccatcctaat tgactggcta gtacaggttc aaatgaaatt 900

caggttgttg caggagacca tgtacatgac tgtctccatt attgatcggt tcatgcagaa 960

taattgtgtg cccaagaaga tgctgcagct ggttggtgtc actgccatgt ttattgcaag 1020

caaatatgaa gaaatgtacc ctccagaaat tggtgacttt gcttttgtga ctgacaacac 1080

ttatactaag caccaaatca gacagatgga aatgaagatt ctaagagctt taaactttgg 1140

tctgggtcgg cctctacctt tgcacttcct tcggagagca tctaagattg gagaggttga 1200

tgtcgagcaa catactttgg ccaaatacct gatggaacta actatgttgg actatgacat 1260

ggtgcacttt cctccttctc aaattgcagc aggagctttt tgcttagcac tgaaaattct 1320

ggataatggt gaatggacac caactctaca acattacctg tcatatactg aagaatctct 1380

tcttccagtt atgcagcacc tggctaagaa tgtagtcatg gtaaatcaag gacttacaaa 1440

gcacatgact gtcaagaaca agtatgccac atcgaagcat gctaagatca gcactctacc 1500

acagctgaat tctgcactag ttcaagattt agccaaggct gtggcaaagg tgtaacttgt 1560

aaacttgagt tggagtacta tatttacaaa taaaattggc accatgtgcc atctgtacat 1620

attactgttg catttacttt taataaagct tgtggcccct tttacttttt tatagcttaa 1680

ctaatttgaa tgtggttact tcctactgta gggtagcgga aaagttgtct taaaaggtat 1740

ggtggggata tttttaaaaa ctccttttgg tttacctggg gatccaattg atgtatatgt 1800

ttatatactg ggttcttgtt ttatatacct ggcttttact ttattaatat gagttactga 1860

aggtgatgga ggtatttgaa aattttactt ccataggaca tactgcatgt aagccaagtc 1920

atggagaatc tgctgcatag ctctatttta aagtaaaagt ctaccaccga atccctagtc 1980

cccctgtttt ctgtttcttc ttgtgattgc tgccataatt ctaagttatt tacttttacc 2040

actatttaag ttatcaactt tagctagtat cttcaaactt tcactttgaa aaatgagaat 2100

tttatattct aagccagttt tcattttggt tttgtgtttt ggttaataaa acaatactca 2160

aatacaaaaa aaaaaaa 2177

<210> 109

<211> 2011

<212> DNA

<213>Homo sapiens

<400> 109

gcggccgcca gcgcggtgta gggggcaggc gcggatcccg ccaccgccgc gcgctcggcc 60

cgccgactcc cggcgccgcc gccgccactg ccgtcgccgc cgccgcctgc cgggactgga 120

gcgcgccgtc cgccgcggac aagaccctgg cctcaggccg gagcagcccc atcatgccga 180

gggagcgcag ggagcgggat gcgaaggagc gggacaccat gaaggaggac ggcggcgcgg 240

agttctcggc tcgctccagg aagaggaagg caaacgtgac cgtttttttg caggatccag 300

atgaagaaat ggccaaaatc gacaggacgg cgagggacca gtgtgggagc cagccttggg 360

acaataatgc agtctgtgca gacccctgct ccctgatccc cacacctgac aaagaagatg 420

atgaccgggt ttacccaaac tcaacgtgca agcctcggat tattgcacca tccagaggct 480

ccccgctgcc tgtactgagc tgggcaaata gagaggaagt ctggaaaatc atgttaaaca 540

aggaaaagac atacttaagg gatcagcact ttcttgagca acaccctctt ctgcagccaa 600

aaatgcgagc aattcttctg gattggttaa tggaggtgtg tgaagtctat aaacttcaca 660

gggagacctt ttacttggca caagatttct ttgaccggta tatggcgaca caagaaaatg 720

ttgtaaaaac tcttttacag cttattggga tttcatcttt atttattgca gccaaacttg 780

aggaaatcta tcctccaaag ttgcaccagt ttgcgtatgt gacagatgga gcttgttcag 840

gagatgaaat tctcaccatg gaattaatga ttatgaaggc ccttaagtgg cgtttaagtc 900

ccctgactat tgtgtcctgg ctgaatgtat acatgcaggt tgcatatcta aatgacttac 960

atgaagtgct actgccgcag tatccccagc aaatctttat acagattgca gagctgttgg 1020

atctctgtgt cctggatgtt gactgccttg aatttcctta tggtatactt gctgcttcgg 1080

ccttgtatca tttctcgtca tctgaattga tgcaaaaggt ttcagggtat cagtggtgcg 1140

acatagagaa ctgtgtcaag tggatggttc catttgccat ggttataagg gagacgggga 1200

gctcaaaact gaagcacttc aggggcgtcg ctgatgaaga tgcacacaac atacagaccc 1260

acagagacag cttggatttg ctggacaaag cccgagcaaa gaaagccatg ttgtctgaac 1320

aaaatagggc ttctcctctc cccagtgggc tcctcacccc gccacagagc ggtaagaagc 1380

agagcagcgg gccggaaatg gcgtgaccac cccatccttc tccaccaaag acagttgcgc 1440

gcctgctcca cgttctcttc tgtctgttgc agcggaggcg tgcgtttgct tttacagata 1500

tctgaatgga agagtgtttc ttccacaaca gaagtatttc tgtggatggc atcaaacagg 1560

gcaaagtgtt ttttattgaa tgcttatagg ttttttttaa ataagtgggt caagtacacc 1620

agccacctcc agacaccagt gcgtgctccc gatgctgcta tggaaggtgc tacttgacct 1680

aagggactcc cacaacaaca aaagcttgaa gctgtggagg gccacggtgg cgtggctctc 1740

ctcgcaggtg ttctgggctc cgttgtacca agtggagcag gtggttgcgg gcaagcgttg 1800

tgcagagccc atagccagct gggcaggggg ctgccctctc cacattatca gttgacagtg 1860

tacaatgcct ttgatgaact gttttgtaag tgctgctata tctatccatt ttttaataaa 1920

gataatactg tttttgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2011

<210> 110

<211> 1737

<212> DNA

<213>Homo sapiens

<400> 110

gagggcacgg gctccgtagg caccaactgc aaggacccct ccccctgcgg gcgctcccat 60

ggcacagttc gcgttcgaga gtgacctgca ctcgctgctt cagctggatg cacccatccc 120

caatgcaccc cctgcgcgct ggcagcgcaa agccaaggaa gccgcaggcc cggccccctc 180

acccatgcgg gccgccaacc gatcccacag cgccggcagg actccgggcc gaactcctgg 240

caaatccagt tccaaggttc agaccactcc tagcaaacct ggcggtgacc gctatatccc 300

ccatcgcagt gctgcccaga tggaggtggc cagcttcctc ctgagcaagg agaaccagcc 360

tgaaaacagc cagacgccca ccaagaagga acatcagaaa gcctgggctt tgaacctgaa 420

cggttttgat gtagaggaag ccaagatcct tcggctcagt ggaaaaacca caaaaatgcg 480

ccagagggtt atcacgaaca gactgaaagt actctacagc caaaaggcca ctcctggctc 540

cagccggaag acctgccgtt tacattcctt ccctgccaag accgtatcct ggatgcgcct 600

gaaatcgaat gactattaac tgaacctgtg ggactggcag tccggggaat gtccgggccg 660

ggccacggcc acgaggtgtt ccgtgtggag tgcaagctgg gacacaccgt gccgcttgtg 720

cacagggcca cgcggggaaa taatcccggg gcgcgcaaag cggcactggc gagagccgca 780

cgggccggtg ctgggggtgg tacaacaggc caaaacaaca cacaaggcca acaagacata 840

cgcgcgctga caccacggtg caaagcgctc agacgagtag taaccggcac tgtggttgct 900

gcctccccac ctctcccgct ctcagcgtaa gataaaagaa agaagagcaa aaagcaaaga 960

aagaagacga gacgagacac acaggaacga acagtaaagc aagctaaagc aaacgcaaga 1020

ccagacaaca gaaatagaaa gaaccaacag agaggagaca gaacaggacg ccagcaacat 1080

agcaacaaac gaacagaaga gagcactaaa caaaagcagc agcaagacga gacaggagag 1140

aaggaggaag gagggccgag cgagcaggga gcgcgagcag cgaggcgaag cagcagacaa 1200

gggcaggcga agggcaacga gaggaggcac cacacaaaaa ggagagggga caggagaagc 1260

agcgagagaa gcggaggagc aacaagagga agaaaaggag agggagagga gggagagagc 1320

ggaaggagga agaaacagca cgaggcgacg aaggggggag acgcgggggc aggaaaagac 1380

acaggaaggc agcgcggagg aggagaaggg gaagcaggaa ggagacggaa ggagaagagg 1440

gagaggacag cgcaagagag cgcgcgcggc gacagcgagg gacggagcga gagagaggaa 1500

acggaaagcg agagggaaga ggagaggcaa cgcagcgaac caaccgaaaa cagcagaaag 1560

agaggagaag gacgcgcaaa gaggcaagcg caagacgaca ggaaacgaag cgagagacga 1620

gaagccggtg acgagcagga gaaagggaag gcaggagaca ggacaggcgg aagagagaca 1680

cgcgagacgc aaagagtgag cagaacgaag cgaagagcaa cgcacgagag aaacgac 1737

<210> 111

<211> 3053

<212> DNA

<213>Homo sapiens

<400> 111

gagcgcggct ggagtttgct gctgccgctg tgcagtttgt tcaggggctt gtggtggtga 60

gtccgagagg ctgcgtgtga gagacgtgag aaggatcctg cactgaggag gtggaaagaa 120

gaggattgct cgaggaggcc tggggtctgt gaggcagcgg agctgggtga aggctgcggg 180

ttccggcgag gcctgagctg tgctgtcgtc atgcctcaaa cccgatccca ggcacaggct 240

acaatcagtt ttccaaaaag gaagctgtct cgggcattga acaaagctaa aaactccagt 300

gatgccaaac tagaaccaac aaatgtccaa accgtaacct gttctcctcg tgtaaaagcc 360

ctgcctctca gccccaggaa acgtctgggc gatgacaacc tatgcaacac tccccattta 420

cctccttgtt ctccaccaaa gcaaggcaag aaagagaatg gtccccctca ctcacataca 480

cttaagggac gaagattggt atttgacaat cagctgacaa ttaagtctcc tagcaaaaga 540

gaactagcca aagttcacca aaacaaaata ctttcttcag ttagaaaaag tcaagagatc 600

acaacaaatt ctgagcagag atgtccactg aagaaagaat ctgcatgtgt gagactattc 660

aagcaagaag gcacttgcta ccagcaagca aagctggtcc tgaacacagc tgtcccagat 720

cggctgcctg ccagggaaag ggagatggat gtcatcagga atttcttgag ggaacacatc 780

tgtgggaaaa aagctggaag cctttacctt tctggtgctc ctggaactgg aaaaactgcc 840

tgcttaagcc ggattctgca agacctcaag aaggaactga aaggctttaa aactatcatg 900

ctgaattgca tgtccttgag gactgcccag gctgtattcc cagctattgc tcaggagatt 960

tgtcaggaag aggtatccag gccagctggg aaggacatga tgaggaaatt ggaaaaacat 1020

atgactgcag agaagggccc catgattgtg ttggtattgg acgagatgga tcaactggac 1080

agcaaaggcc aggatgtatt gtacacgcta tttgaatggc catggctaag caattctcac 1140

ttggtgctga ttggtattgc taataccctg gatctcacag atagaattct acctaggctt 1200

caagctagag aaaaatgtaa gccacagctg ttgaacttcc caccttatac cagaaatcag 1260

atagtcacta ttttgcaaga tcgacttaat caggtatcta gagatcaggt tctggacaat 1320

gctgcagttc aattctgtgc ccgcaaagtc tctgctgttt caggagatgt tcgcaaagca 1380

ctggatgttt gcaggagagc tattgaaatt gtagagtcag atgtcaaaag ccagactatt 1440

ctcaaaccac tgtctgaatg taaatcacct tctgagcctc tgattcccaa gagggttggt 1500

cttattcaca tatcccaagt catctcagaa gttgatggta acaggatgac cttgagccaa 1560

gaaggagcac aagattcctt ccctcttcag cagaagatct tggtttgctc tttgatgctc 1620

ttgatcaggc agttgaaaat caaagaggtc actctgggga agttatatga agcctacagt 1680

aaagtctgtc gcaaacagca ggtggcggct gtggaccagt cagagtgttt gtcactttca 1740

gggctcttgg aagccagggg cattttagga ttaaagagaa acaaggaaac ccgtttgaca 1800

aaggtgtttt tcaagattga agagaaagaa atagaacatg ctctgaaaga taaagcttta 1860

attggaaata tcttagctac tggattgcct taaattcttc tcttacaccc cacccgaaag 1920

tattcagctg gcatttagag agctacagtc ttcattttag tgctttacac attcgggcct 1980

gaaaacaaat atgacctttt ttacttgaag ccaatgaatt ttaatctata gattctttaa 2040

tattagcaca gaataatatc tttgggtctt actattttta cccataaaag tgaccaggta 2100

gacccttttt aattacattc actacttcta ccacttgtgt atctctagcc aatgtgcttg 2160

caagtgtaca gatctgtgta gaggaatgtg tgtatattta cctcttcgtt tgctcaaaca 2220

tgagtgggta tttttttgtt tgtttttttt gttgttgttg tttttgaggc gcgtctcacc 2280

ctgttgccca ggctggagtg caatggcgcg ttctctgctc actacagcac ccgcttccca 2340

ggttgaagtg attctcttgc ctcagcctcc cgagtagctg ggattacagg tgcccaccac 2400

cgcgcccagc taatttttta atttttagta gagacagggt tttaccatgt tggccaggct 2460

ggtcttgaac tcctgaccct caagtgatct gcccaccttg gcctccctaa gtgctgggat 2520

tataggcgtg agccaccatg ctcagccatt aaggtatttt gttaagaact ttaagtttag 2580

ggtaagaaga atgaaaatga tccagaaaaa tgcaagcaag tccacatgga gatttggagg 2640

acactggtta aagaatttat ttctttgtat agtatactat gttcatggtg cagatactac 2700

aacattgtgg cattttagac tcgttgagtt tcttgggcac tcccaagggc gttggggtca 2760

taaggagact ataactctac agattgtgaa tatatttatt ttcaagttgc attctttgtc 2820

tttttaagca atcagatttc aagagagctc aagctttcag aagtcaatgt gaaaattcct 2880

tcctaggctg tcccacagtc tttgctgccc ttagatgaag ccacttgttt caagatgact 2940

actttggggt tgggttttca tctaaacaca tttttccagt cttattagat aaattagtcc 3000

atatggttgg ttaatcaaga gccttctggg tttggtttgg tggcattaaa tgg 3053

<210> 112

<211> 1843

<212> DNA

<213>Homo sapiens

<400> 112

gcggaatggg gcgggacttc cagtaggagg cggcaagttt gaaaagtgat gacggttgac 60

gtttgctgat ttttgacttt gcttgtagct gctccccgaa ctcgccgtct tcctgtcggc 120

ggccggcact gtagattaac aggaaacttc caagatggaa actttgtctt tccccagata 180

taatgtagct gagattgtga ttcatattcg caataagatc ttaacaggag ctgatggtaa 240

aaacctcacc aagaatgatc tttatccaaa tccaaagcct gaagtcttgc acatgatcta 300

catgagagcc ttacaaatag tatatggaat tcgactggaa catttttaca tgatgccagt 360

gaactctgaa gtcatgtatc cacatttaat ggaaggcttc ttaccattca gcaatttagt 420

tactcatctg gactcatttt tgcctatctg ccgggtgaat gactttgaga ctgctgatat 480

tctatgtcca aaagcaaaac ggacaagtcg gtttttaagt ggcattatca actttattca 540

cttcagagaa gcatgccgtg aaacgtatat ggaatttctt tggcaatata aatcctctgc 600

ggacaaaatg caacagttaa acgccgcaca ccaggaggca ttaatgaaac tggagagact 660

tgattctgtt ccagttgaag agcaagaaga gttcaagcag ctttcagatg gaattcagga 720

gctacaacaa tcactaaatc aggattttca tcaaaaaacg atagtgctgc aagagggaaa 780

ttcccaaaag aagtcaaata tttcagagaa aaccaagcgt ttgaatgaac taaaattgtc 840

ggtggtttct ttgaaagaaa tacaagagag tttgaaaaca aaaattgtgg attctccaga 900

gaagttaaag aattataaag aaaaaatgaa agatacggtc cagaagctta aaaatgccag 960

acaagaagtg gtggagaaat atgaaatcta tggagactca gttgactgcc tgccttcatg 1020

tcagttggaa gtgcagttat atcaaaagaa aatacaggac ctttcagata atagggaaaa 1080

attagccagt atcttaaagg agagcctgaa cttggaggac caaattgaga gtgatgagtc 1140

agaactgaag aaattgaaga ctgaagaaaa ttcgttcaaa agactgatga ttgtgaagaa 1200

ggaaaaactt gccacagcac aattcaaaat aaataagaag catgaagatg ttaagcaata 1260

caaacgcaca gtaattgagg attgcaataa agttcaagaa aaaagaggtg ctgtctatga 1320

acgagtaacc acaattaatc aagaaatcca aaaaattaaa cttggaattc aacaactaaa 1380

agatgctgct gaaagggaga aactgaagtc ccaggaaata tttctaaact tgaaaactgc 1440

tttggagaaa taccacgacg gtattgaaaa ggcagcagag gactcctatg ctaagataga 1500

tgagaagaca gctgaactga agaggaagat gttcaaaatg tcaacctgat taacaaaatt 1560

acatgtcttt ttgtaaatgg cttgccatct tttaattttc tatttagaaa gaaaagttga 1620

agcgaatgga agtatcagaa gtaccaaata atgttggctt catcagtttt tatacactct 1680

cataagtagt taataagatg aatttaatgt aggcttttat taatttataa ttaaaataac 1740

ttgtgcagct attcatgtct ctactctgcc ccttgttgta aatagtttga gtaaaacaaa 1800

actagttacc tttgaaatat atatattttt ttctgttact atc 1843

<210> 113

<211> 3686

<212> DNA

<213>Homo sapiens

<400> 113

ggctagcgcg ggaggtggag aaagaggctt gggcggcccc gctgtagccg cgtgtgggag 60

gacgcacggg cctgcttcaa agctttggga taacagcgcc tccgggggat aatgaatgcg 120

gagcctccgt tttcagtcga cttcagatgt gtctccactt ttttccgctg tagccgcaag 180

gcaaggaaac atttctcttc ccgtactgag gaggctgagg agtgcactgg gtgttctttt 240

ctcctctaac ccagaactgc gagacagagg ctgagtccct gtaaagaaca gctccagaaa 300

agccaggaga gcgcaggagg gcatccggga ggccaggagg ggttcgctgg ggcctcaacc 360

gcacccacat cggtcccacc tgcgaggggg cgggacctcg tggcgctgga ccaatcagca 420

cccacctgcg ctcacctggc ctcctcccgc tggctcccgg gggctgcggt gctcaaaggg 480

gcaagagctg agcggaacac cggcccgccg tcgcggcagc tgcttcaccc ctctctctgc 540

agccatgggg ctccctcgtg gacctctcgc gtctctcctc cttctccagg tttgctggct 600

gcagtgcgcg gcctccgagc cgtgccgggc ggtcttcagg gaggctgaag tgaccttgga 660

ggcgggaggc gcggagcagg agcccggcca ggcgctgggg aaagtattca tgggctgccc 720

tgggcaagag ccagctctgt ttagcactga taatgatgac ttcactgtgc ggaatggcga 780

gacagtccag gaaagaaggt cactgaagga aaggaatcca ttgaagatct tcccatccaa 840

acgtatctta cgaagacaca agagagattg ggtggttgct ccaatatctg tccctgaaaa 900

tggcaagggt cccttccccc agagactgaa tcagctcaag tctaataaag atagagacac 960

caagattttc tacagcatca cggggccggg ggcagacagc ccccctgagg gtgtcttcgc 1020

tgtagagaag gagacaggct ggttgttgtt gaataagcca ctggaccggg aggagattgc 1080

caagtatgag ctctttggcc acgctgtgtc agagaatggt gcctcagtgg aggaccccat 1140

gaacatctcc atcatagtga ccgaccagaa tgaccacaag cccaagttta cccaggacac 1200

cttccgaggg agtgtcttag agggagtcct accaggtact tctgtgatgc agatgacagc 1260

cacagatgag gatgatgcca tctacaccta caatggggtg gttgcttact ccatccatag 1320

ccaagaacca aaggacccac acgacctcat gttcacaatt caccggagca caggcaccat 1380

cagcgtcatc tccagtggcc tggaccggga aaaagtccct gagtacacac tgaccatcca 1440

ggccacagac atggatgggg acggctccac caccacggca gtggcagtag tggagatcct 1500

tgatgccaat gacaatgctc ccatgtttga cccccagaag tacgaggccc atgtgcctga 1560

gaatgcagtg ggccatgagg tgcagaggct gacggtcact gatctggacg cccccaactc 1620

accagcgtgg cgtgccacct accttatcat gggcggtgac gacggggacc attttaccat 1680

caccacccac cctgagagca accagggcat cctgacaacc aggaagggtt tggattttga 1740

ggccaaaaac cagcacaccc tgtacgttga agtgaccaac gaggcccctt ttgtgctgaa 1800

gctcccaacc tccacagcca ccatagtggt ccacgtggag gatgtgaatg aggcacctgt 1860

gtttgtccca ccctccaaag tcgttgaggt ccaggagggc atccccactg gggagcctgt 1920

gtgtgtctac actgcagaag accctgacaa ggagaatcaa aagatcagct accgcatcct 1980

gagagaccca gcagggtggc tagccatgga cccagacagt gggcaggtca cagctgtggg 2040

caccctcgac cgtgaggatg agcagtttgt gaggaacaac atctatgaag tcatggtctt 2100

ggccatggac aatggaagcc ctcccaccac tggcacggga acccttctgc taacactgat 2160

tgatgtcaac gaccatggcc cagtccctga gccccgtcag atcaccatct gcaaccaaag 2220

ccctgtgcgc caggtgctga acatcacgga caaggacctg tctccccaca cctccccttt 2280

ccaggcccag ctcacagatg actcagacat ctactggacg gcagaggtca acgaggaagg 2340

tgacacagtg gtcttgtccc tgaagaagtt cctgaagcag gatacatatg acgtgcacct 2400

ttctctgtct gaccatggca acaaagagca gctgacggtg atcagggcca ctgtgtgcga 2460

ctgccatggc catgtcgaaa cctgccctgg accctggaaa ggaggtttca tcctccctgt 2520

gctgggggct gtcctggctc tgctgttcct cctgctggtg ctgcttttgt tggtgagaaa 2580

gaagcggaag atcaaggagc ccctcctact cccagaagat gacacccgtg acaacgtctt 2640

ctactatggc gaagaggggg gtggcgaaga ggaccaggac tatgacatca cccagctcca 2700

ccgaggtctg gaggccaggc cggaggtggt tctccgcaat gacgtggcac caaccatcat 2760

cccgacaccc atgtaccgtc ctaggccagc caacccagat gaaatcggca actttataat 2820

tgagaacctg aaggcggcta acacagaccc cacagccccg ccctacgaca ccctcttggt 2880

gttcgactat gagggcagcg gctccgacgc cgcgtccctg agctccctca cctcctccgc 2940

ctccgaccaa gaccaagatt acgattatct gaacgagtgg ggcagccgct tcaagaagct 3000

ggcagacatg tacggtggcg gggaggacga ctaggcggcc tgcctgcagg gctggggacc 3060

aaacgtcagg ccacagagca tctccaaggg gtctcagttc ccccttcagc tgaggacttc 3120

ggagcttgtc aggaagtggc cgtagcaact tggcggagac aggctatgag tctgacgtta 3180

gagtggttgc ttccttagcc tttcaggatg gaggaatgtg ggcagtttga cttcagcact 3240

gaaaacctct ccacctgggc cagggttgcc tcagaggcca agtttccaga agcctcttac 3300

ctgccgtaaa atgctcaacc ctgtgtcctg ggcctgggcc tgctgtgact gacctacagt 3360

ggactttctc tctggaatgg aaccttctta ggcctcctgg tgcaacttaa tttttttttt 3420

taatgctatc ttcaaaacgt tagagaaagt tcttcaaaag tgcagcccag agctgctggg 3480

cccactggcc gtcctgcatt tctggtttcc agaccccaat gcctcccatt cggatggatc 3540

tctgcgtttt tatactgagt gtgcctaggt tgccccttat tttttatttt ccctgttgcg 3600

ttgctataga tgaagggtga ggacaatcgt gtatatgtac tagaactttt ttattaaaga 3660

aacttttccc aaaaaaaaaa aaaaaa 3686

<210> 114

<211> 10316

<212> DNA

<213>Homo sapiens

<400> 114

gagaccagaa gcgggcgaat tgggcaccgg tggcggctgc gggcagtttg aattagactc 60

tgggctccag cccgccgaag ccgcgccaga actgtactct ccgagaggtc gttttcccgt 120

ccccgagagc aagtttattt acaaatgttg gagtaataaa gaaggcagaa caaaatgagc 180

tgggctttgg aagaatggaa agaagggctg cctacaagag ctcttcagaa aattcaagag 240

cttgaaggac agcttgacaa actgaagaag gaaaagcagc aaaggcagtt tcagcttgac 300

agtctcgagg ctgcgctgca gaagcaaaaa cagaaggttg aaaatgaaaa aaccgagggt 360

acaaacctga aaagggagaa tcaaagattg atggaaatat gtgaaagtct ggagaaaact 420

aagcagaaga tttctcatga acttcaagtc aaggagtcac aagtgaattt ccaggaagga 480

caactgaatt caggcaaaaa acaaatagaa aaactggaac aggaacttaa aaggtgtaaa 540

tctgagcttg aaagaagcca acaagctgcg cagtctgcag atgtctctct gaatccatgc 600

aatacaccac aaaaaatttt tacaactcca ctaacaccaa gtcaatatta tagtggttcc 660

aagtatgaag atctaaaaga aaaatataat aaagaggttg aagaacgaaa aagattagag 720

gcagaggtta aagccttgca ggctaaaaaa gcaagccaga ctcttccaca agccaccatg 780

aatcaccgcg acattgcccg gcatcaggct tcatcatctg tgttctcatg gcagcaagag 840

aagaccccaa gtcatctttc atctaattct caaagaactc caattaggag agatttctct 900

gcatcttact tttctgggga acaagaggtg actccaagtc gatcaacttt gcaaataggg 960

aaaagagatg ctaatagcag tttctttgac aattctagca gtcctcatct tttggatcaa 1020

ttaaaagcgc agaatcaaga gctaagaaac aagattaatg agttggaact acgcctgcaa 1080

ggacatgaaa aagaaatgaa aggccaagtg aataagtttc aagaactcca actccaactg 1140

gagaaagcaa aagtggaatt aattgaaaaa gagaaagttt tgaacaaatg tagggatgaa 1200

ctagtgagaa caacagcaca atacgaccag gcgtcaacca agtatactgc attggaacaa 1260

aaactgaaaa aattgacgga agatttgagt tgtcagcgac aaaatgcaga aagtgccaga 1320

tgttctctgg aacagaaaat taaggaaaaa gaaaaggagt ttcaagagga gctctcccgt 1380

caacagcgtt ctttccaaac actggaccag gagtgcatcc agatgaaggc cagactcacc 1440

caggagttac agcaagccaa gaatatgcac aacgtcctgc aggctgaact ggataaactc 1500

acatcagtaa agcaacagct agaaaacaat ttggaagagt ttaagcaaaa gttgtgcaga 1560

gctgaacagg cgttccaggc gagtcagatc aaggagaatg agctgaggag aagcatggag 1620

gaaatgaaga aggaaaacaa cctccttaag agtcactctg agcaaaaggc cagagaagtc 1680

tgccacctgg aggcagaact caagaacatc aaacagtgtt taaatcagag ccagaatttt 1740

gcagaagaaa tgaaagcgaa gaatacctct caggaaacca tgttaagaga tcttcaagaa 1800

aaaataaatc agcaagaaaa ctccttgact ttagaaaaac tgaagcttgc tgtggctgat 1860

ctggaaaagc agcgagattg ttctcaagac cttttgaaga aaagagaaca tcacattgaa 1920

caacttaatg ataagttaag caagacagag aaagagtcca aagccttgct gagtgcttta 1980

gagttaaaaa agaaagaata tgaagaattg aaagaagaga aaactctgtt ttcttgttgg 2040

aaaagtgaaa acgaaaaact tttaactcag atggaatcag aaaaggaaaa cttgcagagt 2100

aaaattaatc acttggaaac ttgtctgaag acacagcaaa taaaaagtca tgaatacaac 2160

gagagagtaa gaacgctgga gatggacaga gaaaacctaa gtgtcgagat cagaaacctt 2220

cacaacgtgt tagacagtaa gtcagtggag gtagagaccc agaaactagc ttatatggag 2280

ctacagcaga aagctgagtt ctcagatcag aaacatcaga aggaaataga aaatatgtgt 2340

ttgaagactt ctcagcttac tgggcaagtt gaagatctag aacacaagct tcagttactg 2400

tcaaatgaaa taatggacaa agaccggtgt taccaagact tgcatgccga atatgagagc 2460

ctcagggatc tgctaaaatc caaagatgct tctctggtga caaatgaaga tcatcagaga 2520

agtcttttgg cttttgatca gcagcctgcc atgcatcatt cctttgcaaa tataattgga 2580

gaacaaggaa gcatgccttc agagaggagt gaatgtcgtt tagaagcaga ccaaagtccg 2640

aaaaattctg ccatcctaca aaatagagtt gattcacttg aattttcatt agagtctcaa 2700

aaacagatga actcagacct gcaaaagcag tgtgaagagt tggtgcaaat caaaggagaa 2760

atagaagaaa atctcatgaa agcagaacag atgcatcaaa gttttgtggc tgaaacaagt 2820

cagcgcatta gtaagttaca ggaagacact tctgctcacc agaatgttgt tgctgaaacc 2880

ttaagtgccc ttgagaacaa ggaaaaagag ctgcaacttt taaatgataa ggtagaaact 2940

gagcaggcag agattcaaga attaaaaaag agcaaccatc tacttgaaga ctctctaaag 3000

gagctacaac ttttatccga aaccctaagc ttggagaaga aagaaatgag ttccatcatt 3060

tctctaaata aaagggaaat tgaagagctg acccaagaga atgggactct taaggaaatt 3120

aatgcatcct taaatcaaga gaagatgaac ttaatccaga aaagtgagag ttttgcaaac 3180

tatatagatg aaagggagaa aagcatttca gagttatctg atcagtacaa gcaagaaaaa 3240

cttattttac tacaaagatg tgaagaaacc ggaaatgcat atgaggatct tagtcaaaaa 3300

tacaaagcag cacaggaaaa gaattctaaa ttagaatgct tgctaaatga atgcactagt 3360

ctttgtgaaa ataggaaaaa tgagttggaa cagctaaagg aagcatttgc aaaggaacac 3420

caagaattct taacaaaatt agcatttgct gaagaaagaa atcagaatct gatgctagag 3480

ttggagacag tgcagcaagc tctgagatct gagatgacag ataaccaaaa caattctaag 3540

agcgaggctg gtggtttaaa gcaagaaatc atgactttaa aggaagaaca aaacaaaatg 3600

caaaaggaag ttaatgactt attacaagag aatgaacagc tgatgaaggt aatgaagact 3660

aaacatgaat gtcaaaatct agaatcagaa ccaattagga actctgtgaa agaaagagag 3720

agtgagagaa atcaatgtaa ttttaaacct cagatggatc ttgaagttaa agaaatttct 3780

ctagatagtt ataatgcgca gttggtgcaa ttagaagcta tgctaagaaa taaggaatta 3840

aaacttcagg aaagtgagaa ggagaaggag tgcctgcagc atgaattaca gacaattaga 3900

ggagatcttg aaaccagcaa tttgcaagac atgcagtcac aagaaattag tggccttaaa 3960

gactgtgaaa tagatgcgga agaaaagtat atttcagggc ctcatgagtt gtcaacaagt 4020

caaaacgaca atgcacacct tcagtgctct ctgcaaacaa caatgaacaa gctgaatgag 4080

ctagagaaaa tatgtgaaat actgcaggct gaaaagtatg aactcgtaac tgagctgaat 4140

gattcaaggt cagaatgtat cacagcaact aggaaaatgg cagaagaggt agggaaacta 4200

ctaaatgaag ttaaaatatt aaatgatgac agtggtcttc tccatggtga gttagtggaa 4260

gacataccag gaggtgaatt tggtgaacaa ccaaatgaac agcaccctgt gtctttggct 4320

ccattggacg agagtaattc ctacgagcac ttgacattgt cagacaaaga agttcaaatg 4380

cactttgccg aattgcaaga gaaattctta tctttacaaa gtgaacacaa aattttacat 4440

gatcagcact gtcagatgag ctctaaaatg tcagagctgc agacctatgt tgactcatta 4500

aaggccgaaa atttggtctt gtcaacgaat ctgagaaact ttcaaggtga cttggtgaag 4560

gagatgcagc tgggcttgga ggaggggctc gttccatccc tgtcatcctc ttgtgtgcct 4620

gacagctcta gtcttagcag tttgggagac tcctcctttt acagagctct tttagaacag 4680

acaggagata tgtctctttt gagtaattta gaaggggctg tttcagcaaa ccagtgcagt 4740

gtagatgaag tattttgcag cagtctgcag gaggagaatc tgaccaggaa agaaacccct 4800

tcggccccag cgaagggtgt tgaagagctt gagtccctct gtgaggtgta ccggcagtcc 4860

ctcgagaagc tagaagagaa aatggaaagt caagggatta tgaaaaataa ggaaattcaa 4920

gagctcgagc agttattaag ttctgaaagg caagagcttg actgccttag gaagcagtat 4980

ttgtcagaaa atgaacagtg gcaacagaag ctgacaagcg tgactctgga gatggagtcc 5040

aagttggcgg cagaaaagaa acagacggaa caactgtcac ttgagctgga agtagcacga 5100

ctccagctac aaggtctgga cttaagttct cggtctttgc ttggcatcga cacagaagat 5160

gctattcaag gccgaaatga gagctgtgac atatcaaaag aacatacttc agaaactaca 5220

gaaagaacac caaagcatga tgttcatcag atttgtgata aagatgctca gcaggacctc 5280

aatctagaca ttgagaaaat aactgagact ggtgcagtga aacccacagg agagtgctct 5340

ggggaacagt ccccagatac caattatgag cctccagggg aagataaaac ccagggctct 5400

tcagaatgca tttctgaatt gtcattttct ggtcctaatg ctttggtacc tatggatttc 5460

ctggggaatc aggaagatat ccataatctt caactgcggg taaaagagac atcaaatgag 5520

aatttgagat tacttcatgt gatagaggac cgtgacagaa aagttgaaag tttgctaaat 5580

gaaatgaaag aattagactc aaaactccat ttacaggagg tacaactaat gaccaaaatt 5640

gaagcatgca tagaattgga aaaaatagtt ggggaactta agaaagaaaa ctcagattta 5700

agtgaaaaat tggaatattt ttcttgtgat caccaggagt tactccagag agtagaaact 5760

tctgaaggcc tcaattctga tttagaaatg catgcagata aatcatcacg tgaagatatt 5820

ggagataatg tggccaaggt gaatgacagc tggaaggaga gatttcttga tgtggaaaat 5880

gagctgagta ggatcagatc ggagaaagct agcattgagc atgaagccct ctacctggag 5940

gctgacttag aggtagttca aacagagaag ctatgtttag aaaaagacaa tgaaaataag 6000

cagaaggtta ttgtctgcct tgaagaagaa ctctcagtgg tcacaagtga gagaaaccag 6060

cttcgtggag aattagatac tatgtcaaaa aaaaccacgg cactggatca gttgtctgaa 6120

aaaatgaagg agaaaacaca agagcttgag tctcatcaaa gtgagtgtct ccattgcatt 6180

caggtggcag aggcagaggt gaaggaaaag acggaactcc ttcagacttt gtcctctgat 6240

gtgagtgagc tgttaaaaga caaaactcat ctccaggaaa agctgcagag tttggaaaag 6300

gactcacagg cactgtcttt gacaaaatgt gagctggaaa accaaattgc acaactgaat 6360

aaagagaaag aattgcttgt caaggaatct gaaagcctgc aggccagact gagtgaatca 6420

gattatgaaa agctgaatgt ctccaaggcc ttggaggccg cactggtgga gaaaggtgag 6480

ttcgcattga ggctgagctc aacacaggag gaagtgcatc agctgagaag aggcatcgag 6540

aaactgagag ttcgcattga ggccgatgaa aagaagcagc tgcacatcgc agagaaactg 6600

aaagaacgcg agcgggagaa tgattcactt aaggataaag ttgagaacct tgaaagggaa 6660

ttgcagatgt cagaagaaaa ccaggagcta gtgattcttg atgccgagaa ttccaaagca 6720

gaagtagaga ctctaaaaac acaaatagaa gagatggcca gaagcctgaa agtttttgaa 6780

ttagaccttg tcacgttaag gtctgaaaaa gaaaatctga caaaacaaat acaagaaaaa 6840

caaggtcagt tgtcagaact agacaagtta ctctcttcat ttaaaagtct gttagaagaa 6900

aaggagcaag cagagataca gatcaaagaa gaatctaaaa ctgcagtgga gatgcttcag 6960

aatcagttaa aggagctaaa tgaggcagta gcagccttgt gtggtgacca agaaattatg 7020

aaggccacag aacagagtct agacccacca atagaggaag agcatcagct gagaaatagc 7080

attgaaaagc tgagagcccg cctagaagct gatgaaaaga agcagctctg tgtcttacaa 7140

caactgaagg aaagtgagca tcatgcagat ttacttaagg gtagagtgga gaaccttgaa 7200

agagagctag agatagccag gacaaaccaa gagcatgcag ctcttgaggc agagaattcc 7260

aaaggagagg tagagaccct aaaagcaaaa atagaaggga tgacccaaag tctgagaggt 7320

ctggaattag atgttgttac tataaggtca gaaaaagaaa atctgacaaa tgaattacaa 7380

aaagagcaag agcgaatatc tgaattagaa ataataaatt catcatttga aaatattttg 7440

caagaaaaag agcaagagaa agtacagatg aaagaaaaat caagcactgc catggagatg 7500

cttcaaacac aattaaaaga gctcaatgag agagtggcag ccctgcataa tgaccaagaa 7560

gcctgtaagg ccaaagagca gaatcttagt agtcaagtag agtgtcttga acttgagaag 7620

gctcagttgc tacaaggcct tgatgaggcc aaaaataatt atattgtttt gcaatcttca 7680

gtgaatggcc tcattcaaga agtagaagat ggcaagcaga aactggagaa gaaggatgaa 7740

gaaatcagta gactgaaaaa tcaaattcaa gaccaagagc agcttgtctc taaactgtcc 7800

caggtggaag gagagcacca actttggaag gagcaaaact tagaactgag aaatctgaca 7860

gtggaattgg agcagaagat ccaagtgcta caatccaaaa atgcctcttt gcaggacaca 7920

ttagaagtgc tgcagagttc ttacaagaat ctagagaatg agcttgaatt gacaaaaatg 7980

gacaaaatgt cctttgttga aaaagtaaac aaaatgactg caaaggaaac tgagctgcag 8040

agggaaatgc atgagatggc acagaaaaca gcagagctgc aagaagaact cagtggagag 8100

aaaaataggc tagctggaga gttgcagtta ctgttggaag aaataaagag cagcaaagat 8160

caattgaagg agctcacact agaaaatagt gaattgaaga agagcctaga ttgcatgcac 8220

aaagaccagg tggaaaagga agggaaagtg agagaggaaa tagctgaata tcagctacgg 8280

cttcatgaag ctgaaaagaa acaccaggct ttgcttttgg acacaaacaa acagtatgaa 8340

gtagaaatcc agacataccg agagaaattg acttctaaag aagaatgtct cagttcacag 8400

aagctggaga tagacctttt aaagtctagt aaagaagagc tcaataattc attgaaagct 8460

actactcaga ttttggaaga attgaagaaa accaagatgg acaatctaaa atatgtaaat 8520

cagttgaaga aggaaaatga acgtgcccag gggaaaatga agttgttgat caaatcctgt 8580

aaacagctgg aagaggaaaa ggagatactg cagaaagaac tctctcaact tcaagctgca 8640

caggagaagc agaaaacagg tactgttatg gataccaagg tcgatgaatt aacaactgag 8700

atcaaagaac tgaaagaaac tcttgaagaa aaaaccaagg aggcagatga atacttggat 8760

aagtactgtt ccttgcttat aagccatgaa aagttagaga aagctaaaga gatgttagag 8820

acacaagtgg cccatctgtg ttcacagcaa tctaaacaag attcccgagg gtctcctttg 8880

ctaggtccag ttgttccagg accatctcca atcccttctg ttactgaaaa gaggttatca 8940

tctggccaaa ataaagcttc aggcaagagg caaagatcca gtggaatatg ggagaatggt 9000

agaggaccaa cacctgctac cccagagagc ttttctaaaa aaagcaagaa agcagtcatg 9060

agtggtattc accctgcaga agacacggaa ggtactgagt ttgagccaga gggacttcca 9120

gaagttgtaa agaaagggtt tgctgacatc ccgacaggaa agactagccc atatatcctg 9180

cgaagaacaa ccatggcaac tcggaccagc ccccgcctgg ctgcacagaa gttagcgcta 9240

tccccactga gtctcggcaa agaaaatctt gcagagtcct ccaaaccaac agctggtggc 9300

agcagatcac aaaaggtcaa agttgctcag cggagcccag tagattcagg caccatcctc 9360

cgagaaccca ccacgaaatc cgtcccagtc aataatcttc ctgagagaag tccgactgac 9420

agccccagag agggcctgag ggtcaagcga ggccgacttg tccccagccc caaagctgga 9480

ctggagtcca acggcagtga gaactgtaag gtccagtgaa ggcactttgt gtgtcagtac 9540

ccctgggagg tgccagtcat tgaatagata aggctgtgcc tacaggactt ctctttagtc 9600

agggcatgct ttattagtga ggagaaaaca attccttaga agtcttaaat atattgtact 9660

ctttagatct cccatgtgta ggtattgaaa aagtttggaa gcactgatca cctgttagca 9720

ttgccattcc tctactgcaa tgtaaatagt ataaagctat gtatataaag ctttttggta 9780

atatgttaca attaaaatga caagcactat atcacaatct ctgtttgtat gtgggtttta 9840

cactaaaaaa atgcaaaaca cattttattc ttctaattaa cagctcctag gaaaatgtag 9900

acttttgctt tatgatattc tatctgtagt atgaggcatg gaatagtttt gtatcgggaa 9960

tttctcagag ctgagtaaaa tgaaggaaaa gcatgttatg tgtttttaag gaaaatgtgc 10020

acacatatac atgtaggagt gtttatcttt ctcttacaat ctgttttaga catctttgct 10080

tatgaaacct gtacatatgt gtgtgtgggt atgtgtttat ttccagtgag ggctgcaggc 10140

ttcctagagg tgtgctatac catgcgtctg tcgttgtgct tttttctgtt tttagaccaa 10200

ttttttacag ttctttggta agcattgtcg tatctggtga tggattaaca tatagccttt 10260

gttttctaat aaaatagtcg ccttcgtttt ctgtaaaaaa aaaaaaaaaa aaaaaa 10316

<210> 115

<211> 2639

<212> DNA

<213>Homo sapiens

<400> 115

ggcacgaggg gccgacgcga gcgccgcgct tcgcttcagc tgctagctgg cccaagggag 60

gcgaccgcgg agggtggcga ggggcggcca ggacccgcag ccccggggcc gggccggtcc 120

ggaccgccag ggagggcagg tcagtgggca gatcgcgtcc gcgggattca atctctgccc 180

gctctgataa cagtcctttt ccctggcgct cacttcgtgc ctggcacccg gctgggcgcc 240

tcaagaccgt tgtctcttcg atcgcttctt tggacttggc gaccatttca gagatgtctt 300

ccagaagtac caaagattta attaaaagta agtggggatc gaagcctagt aactccaaat 360

ccgaaactac attagaaaaa ttaaagggag aaattgcaca cttaaagaca tcagtggatg 420

aaatcacaag tgggaaagga aagctgactg ataaagagag acacagactt ttggagaaaa 480

ttcgagtcct tgaggctgag aaggagaaga atgcttatca actcacagag aaggacaaag 540

aaatacagcg actgagagac caactgaagg ccagatatag tactaccgca ttgcttgaac 600

agctggaaga gacaacgaga gaaggagaaa ggagggagca ggtgttgaaa gccttatctg 660

aagagaaaga cgtattgaaa caacagttgt ctgctgcaac ctcacgaatt gctgaacttg 720

aaagcaaaac caatacactc cgtttatcac agactgtggc tccaaactgc ttcaactcat 780

caataaataa tattcatgaa atggaaatac agctgaaaga tgctctggag aaaaatcagc 840

agtggctcgt gtatgatcag cagcgggaag tctatgtaaa aggactttta gcaaagatct 900

ttgagttgga aaagaaaacg gaaacagctg ctcattcact cccacagcag acaaaaaagc 960

ctgaatcaga aggttatctt caagaagaga agcagaaatg ttacaacgat ctcttggcaa 1020

gtgcaaaaaa agatcttgag gttgaacgac aaaccataac tcagctgagt tttgaactga 1080

gtgaatttcg aagaaaatat gaagaaaccc aaaaagaagt tcacaattta aatcagctgt 1140

tgtattcaca aagaagggca gatgtgcaac atctggaaga tgataggcat aaaacagaga 1200

agatacaaaa actcagggaa gagaatgata ttgctagggg aaaacttgaa gaagagaaga 1260

agagatccga agagctctta tctcaggtcc agtttcttta cacatctctg ctaaagcagc 1320

aagaagaaca aacaagggta gctctgttgg aacaacagat gcaggcatgt actttagact 1380

ttgaaaatga aaaactcgac cgtcaacatg tgcagcatca attgcatgta attcttaagg 1440

agctccgaaa agcaagaaat caaataacac agttggaatc cttgaaacag cttcatgagt 1500

ttgccatcac agagccatta gtcactttcc aaggagagac tgaaaacaga gaaaaagttg 1560

ccgcctcacc aaaaagtccc actgctgcac tcaatgaaag cctggtggaa tgtcccaagt 1620

gcaatataca gtatccagcc actgagcatc gcgatctgct tgtccatgtg gaatactgtt 1680

caaagtagca aaataagtat ttgttttgat attaaaagat tcaatactgt attttctgtt 1740

agcttgtggg cattttgaat tatatatttc acattttgca taaaactgcc tatctacctt 1800

tgacactcca gcatgctagt gaatcatgta tcttttaggc tgctgtgcat ttctcttggc 1860

agtgatacct ccctgacatg gttcatcatc aggctgcaat gacagaatgt ggtgagcagc 1920

gtctactgag actactaaca ttttgcactg tcaaaatact tggtgaggaa aagatagctc 1980

aggttattgc taatgggtta atgcaccagc aagcaaaata ttttatgttt tgggggtttg 2040

aaaaatcaaa gataattaac caaggatctt aactgtgttc gcatttttta tccaagcact 2100

tagaaaacct acaatcctaa ttttgatgtc cattgttaag aggtggtgat agatactatt 2160

ttttttttca tattgtatag cggttattag aaaagttggg gattttcttg atctttattg 2220

ctgcttacca ttgaaactta acccagctgt gttccccaac tctgttctgc gcacgaaaca 2280

gtatctgttt gaggcataat cttaagtggc cacacacaat gttttctctt atgttatctg 2340

gcagtaactg taacttgaat tacattagca cattctgctt agctaaaatt gttaaaataa 2400

actttaataa acccatgtag ccctctcatt tgattgacag tattttagtt atttttggca 2460

ttcttaaagc tgggcaatgt aatgatcaga tctttgtttg tctgaacagg tatttttata 2520

catgcttttt gtaaaccaaa aacttttaaa tttcttcagg ttttctaaca tgcttaccac 2580

tgggctactg taaatgagaa aagaataaaa ttatttaatg ttttaaaaaa aaaaaaaaa 2639

<210> 116

<211> 2632

<212> DNA

<213>Homo sapiens

<400> 116

ggcggctgag cctgagcggg gatgtagagg cggcggcagc agaggcggca ctggcggcaa 60

gagcagacgc ccgagccgag cgagaagagc ggcagagcct tatcccctga agccgggccc 120

cgcgtcccag ccctgcccag cccgcgccca gccatgcgcg ccgcctgctg agtccgggcg 180

ccgcacgctg agccctccgc ccgcgagccg cgctcagctc gggggtgatt agttgctttt 240

tgttgttttt taatttgggc cgcggggagg gggaggaggg gcaggtgctg caggctcccc 300

cccctccccg cctcgggcca gccgcggcgg cgcgactcgg gctccggacc cgggcactgc 360

tggcggctgg agcggagcgc accgcggcgg tggtgcccag agcggagcgc agctccctgc 420

cccgcccctc cccctcggcc tcgcggcgac ggcggcggtg gcggcttgga cgactcggag 480

agccgagtga agacatttcc acctggacac ctgaccatgt gcctgccctg agcagcgagg 540

cccaccaggc atctctgttg tgggcagcag ggccaggtcc tggtctgtgg accctcggca 600

gttggcaggc tccctctgca gtggggtctg ggcctcggcc ccaccatgtc gagcctcggc 660

ggtggctccc aggatgccgg cggcagtagc agcagcagca ccaatggcag cggtggcagt 720

ggcagcagtg gcccaaaggc aggagcagca gacaagagtg cagtggtggc tgccgccgca 780

ccagcctcag tggcagatga cacaccaccc cccgagcgtc ggaacaagag cggtatcatc 840

agtgagcccc tcaacaagag cctgcgccgc tcccgcccgc tctcccacta ctcttctttt 900

ggcagcagtg gtggtagtgg cggtggcagc atgatgggcg gagagtctgc tgacaaggcc 960

actgcggctg cagccgctgc ctccctgttg gccaatgggc atgacctggc ggcggccatg 1020

gcggtggaca aaagcaaccc tacctcaaag cacaaaagtg gtgctgtggc cagcctgctg 1080

agcaaggcag agcgggccac ggagctggca gccgagggac agctgacgct gcagcagttt 1140

gcgcagtcca cagagatgct gaagcgcgtg gtgcaggagc atctcccgct gatgagcgag 1200

gcgggtgctg gcctgcctga catggaggct gtggcaggtg ccgaagccct caatggccag 1260

tccgacttcc cctacctggg cgctttcccc atcaacccag gcctcttcat tatgaccccg 1320

gcaggtgtgt tcctggccga gagcgcgctg cacatggcgg gcctggctga gtaccccatg 1380

cagggagagc tggcctctgc catcagctcc ggcaagaaga agcggaaacg ctgcggcatg 1440

tgcgcgccct gccggcggcg catcaactgc gagcagtgca gcagttgtag gaatcgaaag 1500

actggccatc agatttgcaa attcagaaaa tgtgaggaac tcaaaaagaa gccttccgct 1560

gctctggaga aggtgatgct tccgacggga gccgccttcc ggtggtttca gtgacggcgg 1620

cggaacccaa agctgccctc tccgtgcaat gtcactgctc gtgtggtctc cagcaaggga 1680

ttcgggcgaa gacaaacgga tgcacccgtc tttagaacca aaaatattct ctcacagatt 1740

tcattcctgt ttttatatat atattttttg ttgtcgtttt aacatctcca cgtccctagc 1800

ataaaaagaa aaagaaaaaa atttaaactg ctttttcgga agaacaacaa caaaaaagag 1860

gtaaagacga atctataaag taccgagact tcctgggcaa agaatggaca atcagtttcc 1920

ttcctgtgtc gatgtcgatg ttgtctgtgc aggagatgca gtttttgtgt agagaatgta 1980

aattttctgt aaccttttga aatctagtta ctaataagca ctactgtaat ttagcacagt 2040

ttaactccac cctcatttaa acttcctttg attctttccg accatgaaat agtgcatagt 2100

ttgcctggag aatccactca cgttcataaa gagaatgttg atggcgccgt gtagaagccg 2160

ctctgtatcc atccacgcgt gcagagctgc cagcagggag ctcacagaag gggagggagc 2220

accaggccag ctgagctgca cccacagtcc cgagactggg atcccccacc ccaacagtga 2280

ttttggaaaa aaaaatgaaa gttctgttcg tttatccatt gcgatctggg gagccccatc 2340

tcgatatttc caatcctggc tacttttctt agagaaaata agtccttttt ttctggcctt 2400

gctaatggca acagaagaaa gggcttcttt gcgtggtccc ctgctggtgg gggtgggtcc 2460

ccagggggcc ccctgcggcc tgggcccccc tgcccacggc cagcttcctg ctgatgaaca 2520

tgctgtttgt attgttttag gaaaccaggc tgttttgtga ataaaacgaa tgcatgtttg 2580

tgtcacgaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2632

<210> 117

<211> 5616

<212> DNA

<213>Homo sapiens

<400> 117

ccccggcgca gcgcggccgc agcagcctcc gccccccgca cggtgtgagc gcccgacgcg 60

gccgaggcgg ccggagtccc gagctagccc cggcggccgc cgccgcccag accggacgac 120

aggccacctc gtcggcgtcc gcccgagtcc ccgcctcgcc gccaacgcca caaccaccgc 180

gcacggcccc ctgactccgt ccagtattga tcgggagagc cggagcgagc tcttcgggga 240

gcagcgatgc gaccctccgg gacggccggg gcagcgctcc tggcgctgct ggctgcgctc 300

tgcccggcga gtcgggctct ggaggaaaag aaagtttgcc aaggcacgag taacaagctc 360

acgcagttgg gcacttttga agatcatttt ctcagcctcc agaggatgtt caataactgt 420

gaggtggtcc ttgggaattt ggaaattacc tatgtgcaga ggaattatga tctttccttc 480

ttaaagacca tccaggaggt ggctggttat gtcctcattg ccctcaacac agtggagcga 540

attcctttgg aaaacctgca gatcatcaga ggaaatatgt actacgaaaa ttcctatgcc 600

ttagcagtct tatctaacta tgatgcaaat aaaaccggac tgaaggagct gcccatgaga 660

aatttacagg aaatcctgca tggcgccgtg cggttcagca acaaccctgc cctgtgcaac 720

gtggagagca tccagtggcg ggacatagtc agcagtgact ttctcagcaa catgtcgatg 780

gacttccaga accacctggg cagctgccaa aagtgtgatc caagctgtcc caatgggagc 840

tgctggggtg caggagagga gaactgccag aaactgacca aaatcatctg tgcccagcag 900

tgctccgggc gctgccgtgg caagtccccc agtgactgct gccacaacca gtgtgctgca 960

ggctgcacag gcccccggga gagcgactgc ctggtctgcc gcaaattccg agacgaagcc 1020

acgtgcaagg acacctgccc cccactcatg ctctacaacc ccaccacgta ccagatggat 1080

gtgaaccccg agggcaaata cagctttggt gccacctgcg tgaagaagtg tccccgtaat 1140

tatgtggtga cagatcacgg ctcgtgcgtc cgagcctgtg gggccgacag ctatgagatg 1200

gaggaagacg gcgtccgcaa gtgtaagaag tgcgaagggc cttgccgcaa agtgtgtaac 1260

ggaataggta ttggtgaatt taaagactca ctctccataa atgctacgaa tattaaacac 1320

ttcaaaaact gcacctccat cagtggcgat ctccacatcc tgccggtggc atttaggggt 1380

gactccttca cacatactcc tcctctggat ccacaggaac tggatattct gaaaaccgta 1440

aaggaaatca cagggttttt gctgattcag gcttggcctg aaaacaggac ggacctccat 1500

gcctttgaga acctagaaat catacgcggc aggaccaagc aacatggtca gttttctctt 1560

gcagtcgtca gcctgaacat aacatccttg ggattacgct ccctcaagga gataagtgat 1620

ggagatgtga taatttcagg aaacaaaaat ttgtgctatg caaatacaat aaactggaaa 1680

aaactgtttg ggacctccgg tcagaaaacc aaaattataa gcaacagagg tgaaaacagc 1740

tgcaaggcca caggccaggt ctgccatgcc ttgtgctccc ccgagggctg ctggggcccg 1800

gagcccaggg actgcgtctc ttgccggaat gtcagccgag gcagggaatg cgtggacaag 1860

tgcaaccttc tggagggtga gccaagggag tttgtggaga actctgagtg catacagtgc 1920

cacccagagt gcctgcctca ggccatgaac atcacctgca caggacgggg accagacaac 1980

tgtatccagt gtgcccacta cattgacggc ccccactgcg tcaagacctg cccggcagga 2040

gtcatgggag aaaacaacac cctggtctgg aagtacgcag acgccggcca tgtgtgccac 2100

ctgtgccatc caaactgcac ctacggatgc actgggccag gtcttgaagg ctgtccaacg 2160

aatgggccta agatcccgtc catcgccact gggatggtgg gggccctcct cttgctgctg 2220

gtggtggccc tggggatcgg cctcttcatg cgaaggcgcc acatcgttcg gaagcgcacg 2280

ctgcggaggc tgctgcagga gagggagctt gtggagcctc ttacacccag tggagaagct 2340

cccaaccaag ctctcttgag gatcttgaag gaaactgaat tcaaaaagat caaagtgctg 2400

ggctccggtg cgttcggcac ggtgtataag ggactctgga tcccagaagg tgagaaagtt 2460

aaaattcccg tcgctatcaa ggaattaaga gaagcaacat ctccgaaagc caacaaggaa 2520

atcctcgatg aagcctacgt gatggccagc gtggacaacc cccacgtgtg ccgcctgctg 2580

ggcatctgcc tcacctccac cgtgcagctc atcacgcagc tcatgccctt cggctgcctc 2640

ctggactatg tccgggaaca caaagacaat attggctccc agtacctgct caactggtgt 2700

gtgcagatcg caaagggcat gaactacttg gaggaccgtc gcttggtgca ccgcgacctg 2760

gcagccagga acgtactggt gaaaacaccg cagcatgtca agatcacaga ttttgggctg 2820

gccaaactgc tgggtgcgga agagaaagaa taccatgcag aaggaggcaa agtgcctatc 2880

aagtggatgg cattggaatc aattttacac agaatctata cccaccagag tgatgtctgg 2940

agctacgggg tgaccgtttg ggagttgatg acctttggat ccaagccata tgacggaatc 3000

cctgccagcg agatctcctc catcctggag aaaggagaac gcctccctca gccacccata 3060

tgtaccatcg atgtctacat gatcatggtc aagtgctgga tgatagacgc agatagtcgc 3120

ccaaagttcc gtgagttgat catcgaattc tccaaaatgg cccgagaccc ccagcgctac 3180

cttgtcattc agggggatga aagaatgcat ttgccaagtc ctacagactc caacttctac 3240

cgtgccctga tggatgaaga agacatggac gacgtggtgg atgccgacga gtacctcatc 3300

ccacagcagg gcttcttcag cagcccctcc acgtcacgga ctcccctcct gagctctctg 3360

agtgcaacca gcaacaattc caccgtggct tgcattgata gaaatgggct gcaaagctgt 3420

cccatcaagg aagacagctt cttgcagcga tacagctcag accccacagg cgccttgact 3480

gaggacagca tagacgacac cttcctccca gtgcctgaat acataaacca gtccgttccc 3540

aaaaggcccg ctggctctgt gcagaatcct gtctatcaca atcagcctct gaaccccgcg 3600

cccagcagag acccacacta ccaggacccc cacagcactg cagtgggcaa ccccgagtat 3660

ctcaacactg tccagcccac ctgtgtcaac agcacattcg acagccctgc ccactgggcc 3720

cagaaaggca gccaccaaat tagcctggac aaccctgact accagcagga cttctttccc 3780

aaggaagcca agccaaatgg catctttaag ggctccacag ctgaaaatgc agaataccta 3840

agggtcgcgc cacaaagcag tgaatttatt ggagcatgac cacggaggat agtatgagcc 3900

ctaaaaatcc agactctttc gatacccagg accaagccac agcaggtcct ccatcccaac 3960

agccatgccc gcattagctc ttagacccac agactggttt tgcaacgttt acaccgacta 4020

gccaggaagt acttccacct cgggcacatt ttgggaagtt gcattccttt gtcttcaaac 4080

tgtgaagcat ttacagaaac gcatccagca agaatattgt ccctttgagc agaaatttat 4140

ctttcaaaga ggtatatttg aaaaaaaaaa aaagtatatg tgaggatttt tattgattgg 4200

ggatcttgga gtttttcatt gtcgctattg atttttactt caatgggctc ttccaacaag 4260

gaagaagctt gctggtagca cttgctaccc tgagttcatc caggcccaac tgtgagcaag 4320

gagcacaagc cacaagtctt ccagaggatg cttgattcca gtggttctgc ttcaaggctt 4380

ccactgcaaa acactaaaga tccaagaagg ccttcatggc cccagcaggc cggatcggta 4440

ctgtatcaag tcatggcagg tacagtagga taagccactc tgtcccttcc tgggcaaaga 4500

agaaacggag gggatggaat tcttccttag acttactttt gtaaaaatgt ccccacggta 4560

cttactcccc actgatggac cagtggtttc cagtcatgag cgttagactg acttgtttgt 4620

cttccattcc attgttttga aactcagtat gctgcccctg tcttgctgtc atgaaatcag 4680

caagagagga tgacacatca aataataact cggattccag cccacattgg attcatcagc 4740

atttggacca atagcccaca gctgagaatg tggaatacct aaggatagca ccgcttttgt 4800

tctcgcaaaa acgtatctcc taatttgagg ctcagatgaa atgcatcagg tcctttgggg 4860

catagatcag aagactacaa aaatgaagct gctctgaaat ctcctttagc catcacccca 4920

accccccaaa attagtttgt gttacttatg gaagatagtt ttctcctttt acttcacttc 4980

aaaagctttt tactcaaaga gtatatgttc cctccaggtc agctgccccc aaaccccctc 5040

cttacgcttt gtcacacaaa aagtgtctct gccttgagtc atctattcaa gcacttacag 5100

ctctggccac aacagggcat tttacaggtg cgaatgacag tagcattatg agtagtgtgg 5160

aattcaggta gtaaatatga aactagggtt tgaaattgat aatgctttca caacatttgc 5220

agatgtttta gaaggaaaaa agttccttcc taaaataatt tctctacaat tggaagattg 5280

gaagattcag ctagttagga gcccaccttt tttcctaatc tgtgtgtgcc ctgtaacctg 5340

actggttaac agcagtcctt tgtaaacagt gttttaaact ctcctagtca atatccaccc 5400

catccaattt atcaaggaag aaatggttca gaaaatattt tcagcctaca gttatgttca 5460

gtcacacaca catacaaaat gttccttttg cttttaaagt aatttttgac tcccagatca 5520

gtcagagccc ctacagcatt gttaagaaag tatttgattt ttgtctcaat gaaaataaaa 5580

ctatattcat ttccactcta aaaaaaaaaa aaaaaa 5616

<210> 118

<211> 4816

<212> DNA

<213>Homo sapiens

<400> 118

gttcccggat ttttgtgggc gcctgccccg cccctcgtcc ccctgctgtg tccatatatc 60

gaggcgatag ggttaaggga aggcggacgc ctgatgggtt aatgagcaaa ctgaagtgtt 120

ttccatgatc ttttttgagt cgcaattgaa gtaccacctc ccgagggtga ttgcttcccc 180

atgcggggta gaacctttgc tgtcctgttc accactctac ctccagcaca gaatttggct 240

tatgcctact caatgtgaag atgatgagga tgaaaacctt tgtgatgatc cacttccact 300

taatgaatgg tggcaaagca aagctatatt caagaccaca tgcaaagcta ctccctgagc 360

aaagagtcac agataaaacg ggggcaccag tagaatggcc aggacaaacg cagtgcagca 420

cagagactca gaccctggca gccatgcctg cgcaggcagt gatgagagtg acatgtactg 480

ttgtggacat gcacaaaagt gagtgtgcac cggcacagac atgaagctgc ggctccctgc 540

cagtcccgag acccacctgg acatgctccg ccacctctac cagggctgcc aggtggtgca 600

gggaaacctg gaactcacct acctgcccac caatgccagc ctgtccttcc tgcaggatat 660

ccaggaggtg cagggctacg tgctcatcgc tcacaaccaa gtgaggcagg tcccactgca 720

gaggctgcgg attgtgcgag gcacccagct ctttgaggac aactatgccc tggccgtgct 780

agacaatgga gacccgctga acaataccac ccctgtcaca ggggcctccc caggaggcct 840

gcgggagctg cagcttcgaa gcctcacaga gatcttgaaa ggaggggtct tgatccagcg 900

gaacccccag ctctgctacc aggacacgat tttgtggaag gacatcttcc acaagaacaa 960

ccagctggct ctcacactga tagacaccaa ccgctctcgg gcctgccacc cctgttctcc 1020

gatgtgtaag ggctcccgct gctggggaga gagttctgag gattgtcaga gcctgacgcg 1080

cactgtctgt gccggtggct gtgcccgctg caaggggcca ctgcccactg actgctgcca 1140

tgagcagtgt gctgccggct gcacgggccc caagcactct gactgcctgg cctgcctcca 1200

cttcaaccac agtggcatct gtgagctgca ctgcccagcc ctggtcacct acaacacaga 1260

cacgtttgag tccatgccca atcccgaggg ccggtataca ttcggcgcca gctgtgtgac 1320

tgcctgtccc tacaactacc tttctacgga cgtgggatcc tgcaccctcg tctgccccct 1380

gcacaaccaa gaggtgacag cagaggatgg aacacagcgg tgtgagaagt gcagcaagcc 1440

ctgtgcccga gtgtgctatg gtctgggcat ggagcacttg cgagaggtga gggcagttac 1500

cagtgccaat atccaggagt ttgctggctg caagaagatc tttgggagcc tggcatttct 1560

gccggagagc tttgatgggg acccagcctc caacactgcc ccgctccagc cagagcagct 1620

ccaagtgttt gagactctgg aagagatcac aggttaccta tacatctcag catggccgga 1680

cagcctgcct gacctcagcg tcttccagaa cctgcaagta atccggggac gaattctgca 1740

caatggcgcc tactcgctga ccctgcaagg gctgggcatc agctggctgg ggctgcgctc 1800

actgagggaa ctgggcagtg gactggccct catccaccat aacacccacc tctgcttcgt 1860

gcacacggtg ccctgggacc agctctttcg gaacccgcac caagctctgc tccacactgc 1920

caaccggcca gaggacgagt gtgtgggcga gggcctggcc tgccaccagc tgtgcgcccg 1980

agggcactgc tggggtccag ggcccaccca gtgtgtcaac tgcagccagt tccttcgggg 2040

ccaggagtgc gtggaggaat gccgagtact gcaggggctc cccagggagt atgtgaatgc 2100

caggcactgt ttgccgtgcc accctgagtg tcagccccag aatggctcag tgacctgttt 2160

tggaccggag gctgaccagt gtgtggcctg tgcccactat aaggaccctc ccttctgcgt 2220

ggcccgctgc cccagcggtg tgaaacctga cctctcctac atgcccatct ggaagtttcc 2280

agatgaggag ggcgcatgcc agccttgccc catcaactgc acccactcct gtgtggacct 2340

ggatgacaag ggctgccccg ccgagcagag agccagccct ctgacgtcca tcatctctgc 2400

ggtggttggc attctgctgg tcgtggtctt gggggtggtc tttgggatcc tcatcaagcg 2460

acggcagcag aagatccgga agtacacgat gcggagactg ctgcaggaaa cggagctggt 2520

ggagccgctg acacctagcg gagcgatgcc caaccaggcg cagatgcgga tcctgaaaga 2580

gacggagctg aggaaggtga aggtgcttgg atctggcgct tttggcacag tctacaaggg 2640

catctggatc cctgatgggg agaatgtgaa aattccagtg gccatcaaag tgttgaggga 2700

aaacacatcc cccaaagcca acaaagaaat cttagacgaa gcatacgtga tggctggtgt 2760

gggctcccca tatgtctccc gccttctggg catctgcctg acatccacgg tgcagctggt 2820

gacacagctt atgccctatg gctgcctctt agaccatgtc cgggaaaacc gcggacgcct 2880

gggctcccag gacctgctga actggtgtat gcagattgcc aaggggatga gctacctgga 2940

ggatgtgcgg ctcgtacaca gggacttggc cgctcggaac gtgctggtca agagtcccaa 3000

ccatgtcaaa attacagact tcgggctggc tcggctgctg gacattgacg agacagagta 3060

ccatgcagat gggggcaagg tgcccatcaa gtggatggcg ctggagtcca ttctccgccg 3120

gcggttcacc caccagagtg atgtgtggag ttatggtgtg actgtgtggg agctgatgac 3180

ttttggggcc aaaccttacg atgggatccc agcccgggag atccctgacc tgctggaaaa 3240

gggggagcgg ctgccccagc cccccatctg caccattgat gtctacatga tcatggtcaa 3300

atgttggatg attgactctg aatgtcggcc aagattccgg gagttggtgt ctgaattctc 3360

ccgcatggcc agggaccccc agcgctttgt ggtcatccag aatgaggact tgggcccagc 3420

cagtcccttg gacagcacct tctaccgctc actgctggag gacgatgaca tgggggacct 3480

ggtggatgct gaggagtatc tggtacccca gcagggcttc ttctgtccag accctgcccc 3540

gggcgctggg ggcatggtcc accacaggca ccgcagctca tctaccagga gtggcggtgg 3600

ggacctgaca ctagggctgg agccctctga agaggaggcc cccaggtctc cactggcacc 3660

ctccgaaggg gctggctccg atgtatttga tggtgacctg ggaatggggg cagccaaggg 3720

gctgcaaagc ctccccacac atgaccccag ccctctacag cggtacagtg aggaccccac 3780

agtacccctg ccctctgaga ctgatggcta cgttgccccc ctgacctgca gcccccagcc 3840

tgaatatgtg aaccagccag atgttcggcc ccagccccct tcgccccgag agggccctct 3900

gcctgctgcc cgacctgctg gtgccactct ggaaaggccc aagactctct ccccagggaa 3960

gaatggggtc gtcaaagacg tttttgcctt tgggggtgcc gtggagaacc ccgagtactt 4020

gacaccccag ggaggagctg cccctcagcc ccaccctcct cctgccttca gcccagcctt 4080

cgacaacctc tattactggg accaggaccc accagagcgg ggggctccac ccagcacctt 4140

caaagggaca cctacggcag agaacccaga gtacctgggt ctggacgtgc cagtgtgaac 4200

cagaaggcca agtccgcaga agccctgatg tgtcctcagg gagcagggaa ggcctgactt 4260

ctgctggcat caagaggtgg gagggccctc cgaccacttc caggggaacc tgccatgcca 4320

ggaacctgtc ctaaggaacc ttccttcctg cttgagttcc cagatggctg gaaggggtcc 4380

agcctcgttg gaagaggaac agcactgggg agtctttgtg gattctgagg ccctgcccaa 4440

tgagactcta gggtccagtg gatgccacag cccagcttgg ccctttcctt ccagatcctg 4500

ggtactgaaa gccttaggga agctggcctg agaggggaag cggccctaag ggagtgtcta 4560

agaacaaaag cgacccattc agagactgtc cctgaaacct agtactgccc cccatgagga 4620

aggaacagca atggtgtcag tatccaggct ttgtacagag tgcttttctg tttagttttt 4680

actttttttg ttttgttttt ttaaagatga aataaagacc cagggggaga atgggtgttg 4740

tatggggagg caagtgtggg gggtccttct ccacacccac tttgtccatt tgcaaatata 4800

ttttggaaaa cagcta 4816

<210> 119

<211> 6466

<212> DNA

<213>Homo sapiens

<400> 119

atggtcataa cagcctcctg tctaccgact cagaacggat tttaccaaaa ctgaaaatgc 60

aggctccatg ctcagaagct ctttaacagg ctcgaaaggt ccatgctcct ttctcctgcc 120

cattctatag cataagaaga cagtctctga gtgataatct tctcttcaag aagaagaaaa 180

ctaggaagga gtaagcacaa agatctcttc acattctccg ggactgcggt accaaatatc 240

agcacagcac ttcttgaaaa aggatgtaga ttttaatctg aactttgaac catcactgag 300

gtggcccgcc ggtttctgag ccttctgccc tgcggggaca cggtctgcac cctgcccgcg 360

gccacggacc atgaccatga ccctccacac caaagcatct gggatggccc tactgcatca 420

gatccaaggg aacgagctgg agcccctgaa ccgtccgcag ctcaagatcc ccctggagcg 480

gcccctgggc gaggtgtacc tggacagcag caagcccgcc gtgtacaact accccgaggg 540

cgccgcctac gagttcaacg ccgcggccgc cgccaacgcg caggtctacg gtcagaccgg 600

cctcccctac ggccccgggt ctgaggctgc ggcgttcggc tccaacggcc tggggggttt 660

ccccccactc aacagcgtgt ctccgagccc gctgatgcta ctgcacccgc cgccgcagct 720

gtcgcctttc ctgcagcccc acggccagca ggtgccctac tacctggaga acgagcccag 780

cggctacacg gtgcgcgagg ccggcccgcc ggcattctac aggccaaatt cagataatcg 840

acgccagggt ggcagagaaa gattggccag taccaatgac aagggaagta tggctatgga 900

atctgccaag gagactcgct actgtgcagt gtgcaatgac tatgcttcag gctaccatta 960

tggagtctgg tcctgtgagg gctgcaaggc cttcttcaag agaagtattc aaggacataa 1020

cgactatatg tgtccagcca ccaaccagtg caccattgat aaaaacagga ggaagagctg 1080

ccaggcctgc cggctccgca aatgctacga agtgggaatg atgaaaggtg ggatacgaaa 1140

agaccgaaga ggagggagaa tgttgaaaca caagcgccag agagatgatg gggagggcag 1200

gggtgaagtg gggtctgctg gagacatgag agctgccaac ctttggccaa gcccgctcat 1260

gatcaaacgc tctaagaaga acagcctggc cttgtccctg acggccgacc agatggtcag 1320

tgccttgttg gatgctgagc cccccatact ctattccgag tatgatccta ccagaccctt 1380

cagtgaagct tcgatgatgg gcttactgac caacctggca gacagggagc tggttcacat 1440

gatcaactgg gcgaagaggg tgccaggctt tgtggatttg accctccatg atcaggtcca 1500

ccttctagaa tgtgcctggc tagagatcct gatgattggt ctcgtctggc gctccatgga 1560

gcacccaggg aagctactgt ttgctcctaa cttgctcttg gacaggaacc agggaaaatg 1620

tgtagagggc atggtggaga tcttcgacat gctgctggct acatcatctc ggttccgcat 1680

gatgaatctg cagggagagg agtttgtgtg cctcaaatct attattttgc ttaattctgg 1740

agtgtacaca tttctgtcca gcaccctgaa gtctctggaa gagaaggacc atatccaccg 1800

agtcctggac aagatcacag acactttgat ccacctgatg gccaaggcag gcctgaccct 1860

gcagcagcag caccagcggc tggcccagct cctcctcatc ctctcccaca tcaggcacat 1920

gagtaacaaa ggcatggagc atctgtacag catgaagtgc aagaacgtgg tgcccctcta 1980

tgacctgctg ctggagatgc tggacgccca ccgcctacat gcgcccacta gccgtggagg 2040

ggcatccgtg gaggagacgg accaaagcca cttggccact gcgggctcta cttcatcgca 2100

ttccttgcaa aagtattaca tcacggggga ggcagagggt ttccctgcca cggtctgaga 2160

gctccctggc tcccacacgg ttcagataat ccctgctgca ttttaccctc atcatgcacc 2220

actttagcca aattctgtct cctgcataca ctccggcatg catccaacac caatggcttt 2280

ctagatgagt ggccattcat ttgcttgctc agttcttagt ggcacatctt ctgtcttctg 2340

ttgggaacag ccaaagggat tccaaggcta aatctttgta acagctctct ttcccccttg 2400

ctatgttact aagcgtgagg attcccgtag ctcttcacag ctgaactcag tctatgggtt 2460

ggggctcaga taactctgtg catttaagct acttgtagag acccaggcct ggagagtaga 2520

cattttgcct ctgataagca ctttttaaat ggctctaaga ataagccaca gcaaagaatt 2580

taaagtggct cctttaattg gtgacttgga gaaagctagg tcaagggttt attatagcac 2640

cctcttgtat tcctatggca atgcatcctt ttatgaaagt ggtacacctt aaagctttta 2700

tatgactgta gcagagtatc tggtgattgt caattcattc cccctatagg aatacaaggg 2760

gcacacaggg aaggcagatc ccctagttgg caagactatt ttaacttgat acactgcaga 2820

ttcagatgtg ctgaaagctc tgcctctggc tttccggtca tgggttccag ttaattcatg 2880

cctcccatgg acctatggag agcagcaagt tgatcttagt taagtctccc tatatgaggg 2940

ataagttcct gatttttgtt tttatttttg tgttacaaaa gaaagccctc cctccctgaa 3000

cttgcagtaa ggtcagcttc aggacctgtt ccagtgggca ctgtacttgg atcttcccgg 3060

cgtgtgtgtg ccttacacag gggtgaactg ttcactgtgg tgatgcatga tgagggtaaa 3120

tggtagttga aaggagcagg ggccctggtg ttgcatttag ccctggggca tggagctgaa 3180

cagtacttgt gcaggattgt tgtggctact agagaacaag agggaaagta gggcagaaac 3240

tggatacagt tctgaggcac agccagactt gctcagggtg gccctgccac aggctgcagc 3300

tacctaggaa cattccttgc agaccccgca ttgccctttg ggggtgccct gggatccctg 3360

gggtagtcca gctcttcttc atttcccagc gtggccctgg ttggaagaag cagctgtcac 3420

agctgctgta gacagctgtg ttcctacaat tggcccagca ccctggggca cgggagaagg 3480

gtggggaccg ttgctgtcac tactcaggct gactggggcc tggtcagatt acgtatgccc 3540

ttggtggttt agagataatc caaaatcagg gtttggtttg gggaagaaaa tcctccccct 3600

tcctcccccg ccccgttccc taccgcctcc actcctgcca gctcatttcc ttcaatttcc 3660

tttgacctat aggctaaaaa agaaaggctc attccagcca cagggcagcc ttccctgggc 3720

ctttgcttct ctagcacaat tatgggttac ttcctttttc ttaacaaaaa agaatgtttg 3780

atttcctctg ggtgacctta ttgtctgtaa ttgaaaccct attgagaggt gatgtctgtg 3840

ttagccaatg acccaggtga gctgctcggg cttctcttgg tatgtcttgt ttggaaaagt 3900

ggatttcatt catttctgat tgtccagtta agtgatcacc aaaggactga gaatctggga 3960

gggcaaaaaa aaaaaaaaag tttttatgtg cacttaaatt tggggacaat tttatgtatc 4020

tgtgttaagg atatgtttaa gaacataatt cttttgttgc tgtttgttta agaagcacct 4080

tagtttgttt aagaagcacc ttatatagta taatatatat ttttttgaaa ttacattgct 4140

tgtttatcag acaattgaat gtagtaattc tgttctggat ttaatttgac tgggttaaca 4200

tgcaaaaacc aaggaaaaat atttagtttt tttttttttt tttgtatact tttcaagcta 4260

ccttgtcatg tatacagtca tttatgccta aagcctggtg attattcatt taaatgaaga 4320

tcacatttca tatcaacttt tgtatccaca gtagacaaaa tagcactaat ccagatgcct 4380

attgttggat actgaatgac agacaatctt atgtagcaaa gattatgcct gaaaaggaaa 4440

attattcagg gcagctaatt ttgcttttac caaaatatca gtagtaatat ttttggacag 4500

tagctaatgg gtcagtgggt tctttttaat gtttatactt agattttctt ttaaaaaaat 4560

taaaataaaa caaaaaaaaa tttctaggac tagacgatgt aataccagct aaagccaaac 4620

aattatacag tggaaggttt tacattattc atccaatgtg tttctattca tgttaagata 4680

ctactacatt tgaagtgggc agagaacatc agatgattga aatgttcgcc caggggtctc 4740

cagcaacttt ggaaatctct ttgtattttt acttgaagtg ccactaatgg acagcagata 4800

ttttctggct gatgttggta ttgggtgtag gaacatgatt taaaaaaaaa ctcttgcctc 4860

tgctttcccc cactctgagg caagttaaaa tgtaaaagat gtgatttatc tggggggctc 4920

aggtatggtg gggaagtgga ttcaggaatc tggggaatgg caaatatatt aagaagagta 4980

ttgaaagtat ttggaggaaa atggttaatt ctgggtgtgc accagggttc agtagagtcc 5040

acttctgccc tggagaccac aaatcaacta gctccattta cagccatttc taaaatggca 5100

gcttcagttc tagagaagaa agaacaacat cagcagtaaa gtccatggaa tagctagtgg 5160

tctgtgtttc ttttcgccat tgcctagctt gccgtaatga ttctataatg ccatcatgca 5220

gcaattatga gaggctaggt catccaaaga gaagacccta tcaatgtagg ttgcaaaatc 5280

taacccctaa ggaagtgcag tctttgattt gatttcccta gtaaccttgc agatatgttt 5340

aaccaagcca tagcccatgc cttttgaggg ctgaacaaat aagggactta ctgataattt 5400

acttttgatc acattaaggt gttctcacct tgaaatctta tacactgaaa tggccattga 5460

tttaggccac tggcttagag tactccttcc cctgcatgac actgattaca aatactttcc 5520

tattcatact ttccaattat gagatggact gtgggtactg ggagtgatca ctaacaccat 5580

agtaatgtct aatattcaca ggcagatctg cttggggaag ctagttatgt gaaaggcaaa 5640

tagagtcata cagtagctca aaaggcaacc ataattctct ttggtgcagg tcttgggagc 5700

gtgatctaga ttacactgca ccattcccaa gttaatcccc tgaaaactta ctctcaactg 5760

gagcaaatga actttggtcc caaatatcca tcttttcagt agcgttaatt atgctctgtt 5820

tccaactgca tttcctttcc aattgaatta aagtgtggcc tcgtttttag tcatttaaaa 5880

ttgttttcta agtaattgct gcctctatta tggcacttca attttgcact gtcttttgag 5940

attcaagaaa aatttctatt cttttttttg catccaattg tgcctgaact tttaaaatat 6000

gtaaatgctg ccatgttcca aacccatcgt cagtgtgtgt gtttagagct gtgcacccta 6060

gaaacaacat attgtcccat gagcaggtgc ctgagacaca gacccctttg cattcacaga 6120

gaggtcattg gttatagaga cttgaattaa taagtgacat tatgccagtt tctgttctct 6180

cacaggtgat aaacaatgct ttttgtgcac tacatactct tcagtgtaga gctcttgttt 6240

tatgggaaaa ggctcaaatg ccaaattgtg tttgatggat taatatgccc ttttgccgat 6300

gcatactatt actgatgtga ctcggttttg tcgcagcttt gctttgttta atgaaacaca 6360

cttgtaaacc tcttttgcac tttgaaaaag aatccagcgg gatgctcgag cacctgtaaa 6420

caattttctc aacctatttg atgttcaaat aaagaattaa actaaa 6466

<210> 120

<211> 3478

<212> DNA

<213>Homo sapiens

<400> 120

aaattgaaag gtcagccttt cgcgcgctgt gtaggcaagt tacccgtgtt ctgcgttgcc 60

ggccgtgggt gctctggcca cagtgagtta ggggcgtcgg agcgggtttc tccaaccgca 120

atcggctccg ctcaagggga ggaggagagt cccttctcgg aaggcctaag gaaacgtgtc 180

gtctggaatg ggcttggggg ccacgcctgc acatctccgc gagacagagg gataaagtga 240

agatggtgct gttattgtta cctcgagtgc cacatgcgac ctctgagata tgtacacagt 300

cattcttact atcgcactca gccattctta ctacgctaaa gaagaaataa ttattcgagg 360

atatttgcct ggcccagaag aaacttatgt aaatttcatg aactattata tccgttttcc 420

tcggagtgag agaaaactct ttttagatat catctgagag aactagtgaa tcccagtcac 480

tgagtggagt tgagagtcta agaacctctg aaatttgaga actgctggac cagagccttt 540

agagctctga taaggtgtca acagggtagt taatttggca ccatggggat acagggattg 600

ctacaattta tcaaagaagc ttcagaaccc atccatgtga ggaagtataa agggcaggta 660

gtagctgtgg atacatattg ctggcttcac aaaggagcta ttgcttgtgc tgaaaaacta 720

gccaaaggtg aacctactga taggtatgta ggattttgta tgaaatttgt aaatatgtta 780

ctatctcatg ggatcaagcc tattctcgta tttgatggat gtactttacc ttctaaaaag 840

gaagtagaga gatctagaag agaaagacga caagccaatc ttcttaaggg aaagcaactt 900

cttcgtgagg ggaaagtctc ggaagctcga gagtgtttca cccggtctat caatatcaca 960

catgccatgg cccacaaagt aattaaagct gcccggtctc agggggtaga ttgcctcgtg 1020

gctccctatg aagctgatgc gcagttggcc tatcttaaca aagcgggaat tgtgcaagcc 1080

ataattacag aggactcgga tctcctagct tttggctgta aaaaggtaat tttaaagatg 1140

gaccagtttg gaaatggact tgaaattgat caagctcggc taggaatgtg cagacagctt 1200

ggggatgtat tcacggaaga gaagtttcgt tacatgtgta ttctttcagg ttgtgactac 1260

ctgtcatcac tgcgtgggat tggattagca aaggcatgca aagtcctaag actagccaat 1320

aatccagata tagtaaaggt tatcaagaaa attggacatt atctcaagat gaatatcacg 1380

gtaccagagg attacatcaa cgggtttatt cgggccaaca ataccttcct ctatcagcta 1440

gtttttgatc ccatcaaaag gaaacttatt cctctgaacg cctatgaaga tgatgttgat 1500

cctgaaacac taagctacgc tgggcaatat gttgatgatt ccatagctct tcaaatagca 1560

cttggaaata aagatataaa tacttttgaa cagatcgatg actacaatcc agacactgct 1620

atgcctgccc attcaagaag tcatagttgg gatgacaaaa catgtcaaaa gtcagctaat 1680

gttagcagca tttggcatag gaattactct cccagaccag agtcgggtac tgtttcagat 1740

gccccacaat tgaaggaaaa tccaagtact gtgggagtgg aacgagtgat tagtactaaa 1800

gggttaaatc tcccaaggaa atcatccatt gtgaaaagac caagaagtgc agagctgtca 1860

gaagatgacc tgttgagtca gtattctctt tcatttacga agaagaccaa gaaaaatagc 1920

tctgaaggca ataaatcatt gagcttttct gaagtgtttg tgcctgacct ggtaaatgga 1980

cctactaaca aaaagagtgt aagcactcca cctaggacga gaaataaatt tgcaacattt 2040

ttacaaagga aaaatgaaga aagtggtgca gttgtggttc cagggaccag aagcaggttt 2100

ttttgcagtt cagattctac tgactgtgta tcaaacaaag tgagcatcca gcctctggat 2160

gaaactgctg tcacagataa agagaacaat ctgcatgaat cagagtatgg agaccaagaa 2220

ggcaagagac tggttgacac agatgtagca cgtaattcaa gtgatgacat tccgaataat 2280

catattccag gtgatcatat tccagacaag gcaacagtgt ttacagatga agagtcctac 2340

tcttttgaga gcagcaaatt tacaaggacc atttcaccac ccactttggg aacactaaga 2400

agttgtttta gttggtctgg aggtcttgga gatttttcaa gaacgccgag cccctctcca 2460

agcacagcat tgcagcagtt ccgaagaaag agcgattccc ccacctcttt gcctgagaat 2520

aatatgtctg atgtgtcgca gttaaagagc gaggagtcca gtgacgatga gtctcatccc 2580

ttacgagaag aggcatgttc ttcacagtcc caggaaagtg gagaattctc actgcagagt 2640

tcaaatgcat caaagctttc tcagtgctct agtaaggact ctgattcaga ggaatctgat 2700

tgcaatatta agttacttga cagtcaaagt gaccagacct ccaagctacg tttatctcat 2760

ttctcaaaaa aagacacacc tctaaggaac aaggttcctg ggctatataa gtccagttct 2820

gcagactctc tttctacaac caagatcaaa cctctaggac ctgccagagc cagtgggctg 2880

agcaagaagc cggcaagcat ccagaagaga aagcatcata atgccgagaa caagccgggg 2940

ttacagatca aactcaatga gctctggaaa aactttggat ttaaaaaaga ttctgaaaag 3000

cttcctcctt gtaagaaacc cctgtcccca gtcagagata acatccaact aactccagaa 3060

gcggaagagg atatatttaa caaacctgaa tgtggccgtg ttcaaagagc aatattccag 3120

taaatgcaga ctgctgcaaa gcttttgcct gcaagagaat ctgatcaatt tgaagtccct 3180

gtttgggaat gaggcactta tcagcatgaa gaattttttc tcattctgtg ccattttaaa 3240

aatagaatac attttgtata ttaactttat aattgggttg tggttttttt gctcagcttt 3300

ttatattttt ataagaagct aaatagaaga ataattgtat ctctgacagg tttttggagg 3360

ttttagtgtt aattgggaaa atcctctgga gtttataaaa gtctactcta aatatttctg 3420

taatgttgtc aagtagaaag atagtaaatg gagaaactac aaaaaaaaaa aaaaaaaa 3478

<210> 121

<211> 5192

<212> DNA

<213>Homo sapiens

<400> 121

ccatgacctg ccttgagaag gggcagggga agccagatgg actggaagtg gagtggcagt 60

gaccaaggag gaggaggtgt gataggcttc ccacgcaggg tagatccaga gacaccagtg 120

ccacccatag gcccctagga ctgcagtggt cacccgattc ctttgtccca gctgagactc 180

agttctgagt gttctatttt ggggaacaga ggcgtccttg gtagcatttg gaagaggata 240

gccagctggg gtgtgtgtac atcacagcct gacagtaaca gcatccgaac cagaggtgac 300

tggctaaggg cagacccagg gcaacaggtt aaccgttcta gggccgggca cagggaggag 360

aacattccaa cactctgtgt gcccagtgcc gacgcacgtt ctctctttta tcctcaaaac 420

agtcctatga ggatataagc cagagagaga cagagacaag gaattacaag ttggtgagag 480

tcaggatttg aacttggctc tggcagatgg aaaattaggg tctgtattct ttacaaaacc 540

gtgtgtgcct cagatggagt tggtgcataa caagcagagg tatccagggt cgcggtcctg 600

cttgccacgg aaggggccgc cttgtcagtt gtgaccaccc agccctggaa atgtcagtaa 660

tgctgtaagg agtggggatc ggatcagatg ccatccagat gctgaagttt gaccttgtgt 720

catttttcac tttctttttt ggctcttctg caatcaattc atttatttag caaaaaagaa 780

attatgtgtg ccgagagcat gcagaagata tgtctccgtt ctctgcttcc ctccaaaaaa 840

gaatcccaaa actgctttct gtgaacgtgt gccagggtcc cagcaggact cagggagagc 900

aggaagccca gcccagaccc cttgcacaac ctaccgtggg gaggccttag gctctggcta 960

ctacagagct ggttccagtc tgcactgcca cagcctggcc agggacttgg acacatctgc 1020

tggccacttc ctgtctcagt ttccttatct gcaaaataag ggaaaagccc ccacaaaggt 1080

gcacgtgtag caggagctct tttccctccc tattttagga aggcagttgg tgggaagtcc 1140

agcttgggtc cctgagagct gtgagaagga gatgcggctg ctgctggccc tgttgggggt 1200

cctgctgagt gtgcctgggc ctccagtctt gtccctggag gcctctgagg aagtggagct 1260

tggtatggct tctgaggtgg gagagggtgg caggggtggg aagagtgggc accaggaggg 1320

ggctgctggg ctgagcaaag ctggaaagga tccttgccca ggccctgaga aggtggcggc 1380

agggcagggc tcaaccactg agactcagtc agtgcctggc ttccagcaag cattcatcta 1440

tcactgtgtc tgcgagagag gactggcctt gcagggcgca gggccctaag ctgggctgca 1500

gagctggtgg tgagctcctt gcctgggtgt gtgtgcgtgt gtgtgtgtgt tctgtgcact 1560

gggtgtgtga cctaggaggt ccaggcagca tgtgtggtat aagcattatg agggtgatat 1620

gccccggtgc agcatgaccc tgtatgtggc accaacagca tgtgccttgt gtgtgtgtgt 1680

gtccgtatgt gtgtgtgtgt atgcgtgtgt gtgtgtgtgt gtgtgtgtct tggccactgt 1740

catgtgcact aaatgctgtg tgtgtgacat gccccaagag tgtggcattt gccctgggtg 1800

tggcatccgc agcatgtggc tgtgtgggtg tcaaggagtg gtggctcctt cagcatgcgt 1860

tgcgaagtgc ttgtgccctg catgtgcggt gtgttctctg tacacaggag gctgcctcag 1920

atggggctgc ggggtctgct gacctctgcc ctctgcccac agagccctgc ctggctccca 1980

gcctggagca gcaagagcag gagctgacag tagcccttgg gcagcctgtg cggctgtgct 2040

gtgggcgggc tgagcgtggt ggccactggt acaaggaggg cagtcgcctg gcacctgctg 2100

gccgtgtacg gggctggagg ggccgcctag agattgccag cttcctacct gaggatgctg 2160

gccgctacct ctgcctggca cgaggctcca tgatcgtcct gcagaatctc accttgatta 2220

caggtgactc cttgacctcc agcaacgatg atgaggaccc caagtcccat agggacctct 2280

cgaataggca cagttacccc cagcaaggtc agtaggtctc caaggacttg tgtccccgct 2340

gctgctcatc tgatcactga gaagaggagg cctgtgtggg aacacacggt cattctaggg 2400

gccttcccct gccctccagc accctactgg acacaccccc agcgcatgga gaagaaactg 2460

catgcagtac ctgcggggaa caccgtcaag ttccgctgtc cagctgcagg caaccccacg 2520

cccaccatcc gctggcttaa ggatggacag gcctttcatg gggagaaccg cattggaggc 2580

attcggctgc gccatcagca ctggagtctc gtgatggaga gcgtggtgcc ctcggaccgc 2640

ggcacataca cctgcctggt agagaacgct gtgggcagca tccgttataa ctacctgcta 2700

gatgtgctgg agcggtcccc gcaccggccc atcctgcagg ccgggctccc ggccaacacc 2760

acagccgtgg tgggcagcga cgtggagctg ctgtgcaagg tgtacagcga tgcccagccc 2820

cacatccagt ggctgaagca catcgtcatc aacggcagca gcttcggagc cgacggtttc 2880

ccctatgtgc aagtcctaaa gactgcagac atcaatagct cagaggtgga ggtcctgtac 2940

ctgcggaacg tgtcagccga ggacgcaggc gagtacacct gcctcgcagg caattccatc 3000

ggcctctcct accagtctgc ctggctcacg gtgctgccag gtgagcacct gaagggccag 3060

gagatgctgc gagatgcccc tctgggccag cagtgggggc tgtggcctgt tgggtggtca 3120

gtctctgttg gcctgtgggg tctggcctgg ggggcagtgt gtggatttgt gggtttgagc 3180

tgtatgacag cccctctgtg cctctccaca cgtggccgtc catgtgaccg tctgctgagg 3240

tgtgggtgcc tgggactggg cataactaca gcttcctccg tgtgtgtccc cacatatgtt 3300

gggagctggg agggactgag ttagggtgca cggggcggcc agtctcacca ctgaccagtt 3360

tgtctgtctg tgtgtgtcca tgtgcgaggg cagaggagga ccccacatgg accgcagcag 3420

cgcccgaggc caggtatacg gacatcatcc tgtacgcgtc gggctccctg gccttggctg 3480

tgctcctgct gctggccagg ctgtatcgag ggcaggcgct ccacggccgg cacccccgcc 3540

cgcccgccac tgtgcagaag ctctcccgct tccctctggc ccgacagttc tccctggagt 3600

caggctcttc cggcaagtca agctcatccc tggtacgagg cgtgcgtctc tcctccagcg 3660

gccccgcctt gctcgccggc ctcgtgagtc tagatctacc tctcgaccca ctatgggagt 3720

tcccccggga caggctggtg cttgggaagc ccctaggcga gggctgcttt ggccaggtag 3780

tacgtgcaga ggcctttggc atggaccctg cccggcctga ccaagccagc actgtggccg 3840

tcaagatgct caaagacaac gcctctgaca aggacctggc cgacctggtc tcggagatgg 3900

aggtgatgaa gctgatcggc cgacacaaga acatcatcaa cctgcttggt gtctgcaccc 3960

aggaagggcc cctgtacgtg atcgtggagt gcgccgccaa gggaaacctg cgggagttcc 4020

tgcgggcccg gcgcccccca ggccccgacc tcagccccga cggtcctcgg agcagtgagg 4080

ggccgctctc cttcccagtc ctggtctcct gcgcctacca ggtggcccga ggcatgcagt 4140

atctggagtc ccggaagtgt atccaccggg acctggctgc ccgcaatgtg ctggtgactg 4200

aggacaatgt gatgaagatt gctgactttg ggctggcccg cggcgtccac cacattgact 4260

actataagaa aaccagcaac ggccgcctgc ctgtgaagtg gatggcgccc gaggccttgt 4320

ttgaccgggt gtacacacac cagagtgacg tgtggtcttt tgggatcctg ctatgggaga 4380

tcttcaccct cgggggctcc ccgtatcctg gcatcccggt ggaggagctg ttctcgctgc 4440

tgcgggaggg acatcggatg gaccgacccc cacactgccc cccagagctg tacgggctga 4500

tgcgtgagtg ctggcacgca gcgccctccc agaggcctac cttcaagcag ctggtggagg 4560

cgctggacaa ggtcctgctg gccgtctctg aggagtacct cgacctccgc ctgaccttcg 4620

gaccctattc cccctctggt ggggacgcca gcagcacctg ctcctccagc gattctgtct 4680

tcagccacga ccccctgcca ttgggatcca gctccttccc cttcgggtct ggggtgcaga 4740

catgagcaag gctcaaggct gtgcaggcac ataggctggt ggccttgggc cttggggctc 4800

agccacagcc tgacacagtg ctcgaccttg atagcatggg gcccctggcc cagagttgct 4860

gtgccgtgtc caagggccgt gcccttgccc ttggagctgc cgtgcctgtg tcctgatggc 4920

ccaaatgtca gggttctgct cggcttcttg gaccttggcg cttagtcccc atcccgggtt 4980

tggctgagcc tggctggaga gctgctatgc taaacctcct gcctcccaat accagcagga 5040

ggttctgggc ctctgaaccc cctttcccca cacctccccc tgctgctgct gccccagcgt 5100

cttgacggga gcattggccc ctgagcccag agaagctgga agcctgccga aaacaggagc 5160

aaatggcgtt ttataaatta tttttttgaa at 5192

<210> 122

<211> 3124

<212> DNA

<213>Homo sapiens

<400> 122

taagatccac atcagctcaa ctgcacttgc ctcgcagagg cagcccgctc acttcccgcg 60

gaggcgctcc ccggcgccgc gctccgcggc agccgcctgc ccccggcgct gcccccgccc 120

gccgcgccgc cgccgccgcc gcgcacgccg cgccccgcag ctctgggctt cctcttcgcc 180

cgggtggcgt tgggcccgcg cgggcgctcg ggtgactgca gctgctcagc tcccctcccc 240

cgccccgcgc cgcgcggccg cccgtcgctt cgcacagggc tggatggttg tattgggcag 300

ggtggctcca ggatgttagg aactgtgaag atggaagggc atgaaaccag cgactggaac 360

agctactacg cagacacgca ggaggcctac tcctccgtcc cggtcagcaa catgaactca 420

ggcctgggct ccatgaactc catgaacacc tacatgacca tgaacaccat gactacgagc 480

ggcaacatga ccccggcgtc cttcaacatg tcctatgcca acccgggcct aggggccggc 540

ctgagtcccg gcgcagtagc cggcatgccg gggggctcgg cgggcgccat gaacagcatg 600

actgcggccg gcgtgacggc catgggtacg gcgctgagcc cgagcggcat gggcgccatg 660

ggtgcgcagc aggcggcctc catgaatggc ctgggcccct acgcggccgc catgaacccg 720

tgcatgagcc ccatggcgta cgcgccgtcc aacctgggcc gcagccgcgc gggcggcggc 780

ggcgacgcca agacgttcaa gcgcagctac ccgcacgcca agccgcccta ctcgtacatc 840

tcgctcatca ccatggccat ccagcaggcg cccagcaaga tgctcacgct gagcgagatc 900

taccagtgga tcatggacct cttcccctat taccggcaga accagcagcg ctggcagaac 960

tccatccgcc actcgctgtc cttcaatgac tgcttcgtca aggtggcacg ctccccggac 1020

aagccgggca agggctccta ctggacgctg cacccggact ccggcaacat gttcgagaac 1080

ggctgctact tgcgccgcca gaagcgcttc aagtgcgaga agcagccggg ggccggcggc 1140

gggggcggga gcggaagcgg gggcagcggc gccaagggcg gccctgagag ccgcaaggac 1200

ccctctggcg cctctaaccc cagcgccgac tcgcccctcc atcggggtgt gcacgggaag 1260

accggccagc tagagggcgc gccggccccc gggcccgccg ccagccccca gactctggac 1320

cacagtgggg cgacggcgac agggggcgcc tcggagttga agactccagc ctcctcaact 1380

gcgcccccca taagctccgg gcccggggcg ctggcctctg tgcccgcctc tcacccggca 1440

cacggcttgg caccccacga gtcccagctg cacctgaaag gggaccccca ctactccttc 1500

aaccacccgt tctccatcaa caacctcatg tcctcctcgg agcagcagca taagctggac 1560

ttcaaggcat acgaacaggc actgcaatac tcgccttacg gctctacgtt gcccgccagc 1620

ctgcctctag gcagcgcctc ggtgaccacc aggagcccca tcgagccctc agccctggag 1680

ccggcgtact accaaggtgt gtattccaga cccgtcctaa acacttccta gctcccggga 1740

ctggggggtt tgtctggcat agccatgctg gtagcaagag agaaaaaatc aacagcaaac 1800

aaaaccacac aaaccaaacc gtcaacagca taataaaatc ccaacaacta tttttatttc 1860

atttttcatg cacaaccttt cccccagtgc aaaagactgt tactttatta ttgtattcaa 1920

aattcattgt gtatattact acaaagacaa ccccaaacca atttttttcc tgcgaagttt 1980

aatgatccac aagtgtatat atgaaattct cctccttcct tgcccccctc tctttcttcc 2040

ctctttcccc tccagacatt ctagtttgtg gagggttatt taaaaaaaca aaaaaggaag 2100

atggtcaagt ttgtaaaata tttgtttgtg ctttttcccc ctccttacct gaccccctac 2160

gagtttacag gtctgtggca atactcttaa ccataagaat tgaaatggtg aagaaacaag 2220

tatacactag aggctcttaa aagtattgaa agacaatact gctgttatat agcaagacat 2280

aaacagatta taaacatcag agccatttgc ttctcagttt acatttctga tacatgcaga 2340

tagcagatgt ctttaaatga aatacatgta tattgtgtat ggacttaatt atgcacatgc 2400

tcagatgtgt agacatcctc cgtatattta cataacatat agaggtaata gataggtgat 2460

atacatgata cattctcaag agttgcttga ccgaaagtta caaggacccc aacccctttg 2520

tcctctctac ccacagatgg ccctgggaat caattcctca ggaattgccc tcaagaactc 2580

tgcttcttgc tttgcagagt gccatggtca tgtcattctg aggtcacata acacataaaa 2640

ttagtttcta tgagtgtata ccatttaaag aatttttttt tcagtaaaag ggaatattac 2700

aatgttggag gagagataag ttatagggag ctggatttca aaacgtggtc caagattcaa 2760

aaatcctatt gatagtggcc attttaatca ttgccatcgt gtgcttgttt catccagtgt 2820

tatgcacttt ccacagttgg acatggtgtt agtatagcca gacgggtttc attattattt 2880

ctctttgctt tctcaatgtt aatttattgc atggtttatt ctttttcttt acagctgaaa 2940

ttgctttaaa tgatggttaa aattacaaat taaattgtta atttttatca atgtgattgt 3000

aattaaaaat attttgattt aaataacaaa aataatacca gattttaagc cgtggaaaat 3060

gttcttgatc atttgcagtt aaggacttta aataaatcaa atgttaacaa aaaaaaaaaa 3120

aaaa 3124

<210> 123

<211> 3452

<212> DNA

<213>Homo sapiens

<400> 123

atgcaggcgc gctactccgt gtccagcccc aactccctgg gagtggtgcc ctacctcggc 60

ggcgagcaga gctactaccg cgcggcggcc gcggcggccg ggggcggcta caccgccatg 120

ccggccccca tgagcgtgta ctcgcaccct gcgcacgccg agcagtaccc gggcggcatg 180

gcccgcgcct acgggcccta cacgccgcag ccgcagccca aggacatggt gaagccgccc 240

tatagctaca tcgcgctcat caccatggcc atccagaacg ccccggacaa gaagatcacc 300

ctgaacggca tctaccagtt catcatggac cgcttcccct tctaccggga caacaagcag 360

ggctggcaga acagcatccg ccacaacctc tcgctcaacg agtgcttcgt caaggtgccg 420

cgcgacgaca agaagccggg caagggcagc tactggacgc tggacccgga ctcctacaac 480

atgttcgaga acggcagctt cctgcggcgg cggcggcgct tcaagaagaa ggacgcggtg 540

aaggacaagg aggagaagga caggctgcac ctcaaggagc cgcccccgcc cggccgccag 600

cccccgcccg cgccgccgga gcaggccgac ggcaacgcgc ccggtccgca gccgccgccc 660

gtgcgcatcc aggacatcaa gaccgagaac ggtacgtgcc cctcgccgcc ccagcccctg 720

tccccggccg ccgccctggg cagcggcagc gccgccgcgg tgcccaagat cgagagcccc 780

gacagcagca gcagcagcct gtccagcggg agcagccccc cgggcagcct gccgtcggcg 840

cggccgctca gcctggacgg tgcggattcc gcgccgccgc cgcccgcgcc ctccgccccg 900

ccgccgcacc atagccaggg cttcagcgtg gacaacatca tgacgtcgct gcgggggtcg 960

ccgcagagcg cggccgcgga gctcagctcc ggccttctgg cctcggcggc cgcgtcctcg 1020

cgcgcgggga tcgcaccccc gctggcgctc ggcgcctact cgcccggcca gagctccctc 1080

tacagctccc cctgcagcca gacctccagc gcgggcagct cgggcggcgg cggcggcggc 1140

gcgggggccg cggggggcgc gggcggcgcc gggacctacc actgcaacct gcaagccatg 1200

agcctgtacg cggccggcga gcgcgggggc cacttgcagg gcgcgcccgg gggcgcgggc 1260

ggctcggccg tggacgaccc cctgcccgac tactctctgc ctccggtcac cagcagcagc 1320

tcgtcgtccc tgagtcacgg cggcggcggc ggcggcggcg ggggaggcca ggaggccggc 1380

caccaccctg cggcccacca aggccgcctc acctcgtggt acctgaacca ggcgggcgga 1440

gacctgggcc acttggcgag cgcggcggcg gcggcggcgg ccgcaggcta cccgggccag 1500

cagcagaact tccactcggt gcgggagatg ttcgagtcac agaggatcgg cttgaacaac 1560

tctccagtga acgggaatag tagctgtcaa atggccttcc cttccagcca gtctctgtac 1620

cgcacgtccg gagctttcgt ctacgactgt agcaagtttt gacacaccct caaagccgaa 1680

ctaaatcgaa ccccaaagca ggaaaagcta aaggaaccca tcaaggcaaa atcgaaacta 1740

aaaaaaaaaa atccaattaa aaaaaacccc tgagaatatt caccacacca gcgaacagaa 1800

tatccctcca aaaattcagc tcaccagcac cagcacgaag aaaactctat tttcttaacc 1860

gattaattca gagccacctc cactttgcct tgtctaaata aacaaacccg taaactgttt 1920

tatacagaga cagcaaaatc ttggtttatt aaaggacagt gttactccag ataacacgta 1980

agtttcttct tgcttttcag agacctgctt tcccctcctc ccgtctcccc tctcttgcct 2040

tcttccttgc ctctcacctg taagatatta ttttatccta tgttgaaggg agggggaaag 2100

tccccgttta tgaaagtcgc tttcttttta ttcatggact tgttttaaaa tgtaaattgc 2160

aacatagtaa tttattttta atttgtagtt ggatgtcgtg gaccaaacgc cagaaagtgt 2220

tcccaaaacc tgacgttaaa ttgcctgaaa ctttaaattg tgcttttttt ctcattataa 2280

aaagggaaac tgtattaatc ttattctatc ctcttttctt tctttttgtt gaacatattc 2340

attgtttgtt tattaataaa ttaccattca gtttgaatga gacctatatg tctggatact 2400

ttaatagagc tttaattatt acgaaaaaag atttcagaga taaaacacta gaagttacct 2460

attctccacc taaatctctg aaaaatggag aaaccctctg actagtccat gtcaaatttt 2520

actaaaagtc tttttgttta gatttatttt cctgcagcat cttctgcaaa atgtactata 2580

tagtcagctt gctttgaggc tagtaaaaag atatttttct aaacagattg gagttggcat 2640

ataaacaaat acgttttctc actaatgaca gtccatgatt cggaaatttt aagcccatga 2700

atcagccgcg gtcttaccac ggtgatgcct gtgtgccgag agatgggact gtgcggccag 2760

atatgcacag ataaatattt ggcttgtgta ttccatataa aattgcagtg catattatac 2820

atccctgtga gccagatgct gaatagatat tttcctatta tttcagtcct ttataaaagg 2880

aaaaataaac cagtttttaa atgtatgtat ataattctcc cccatttaca atccttcatg 2940

tattacatag aaggattgct tttttaaaaa tatactgcgg gttggaaagg gatatttaat 3000

ctttgagaaa ctattttaga aaatatgttt gtagaacaat tatttttgaa aaagatttaa 3060

agcaataaca agaaggaagg cgagaggagc agaacatttt ggtctagggt ggtttctttt 3120

taaaccattt tttcttgtta atttacagtt aaacctaggg gacaatccgg attggccctc 3180

ccccttttgt aaataaccca ggaaatgtaa taaattcatt atcttagggt gatctgccct 3240

gccaatcaga ctttggggag atggcgattt gattacagac gttcgggggg gtggggggct 3300

tgcagtttgt tttggagata atacagtttc ctgctatctg ccgctcctat ctagaggcaa 3360

cacttaagca gtaattgctg ttgcttgttg tcaaaatttg atcattgtta aaggattgct 3420

gcaaataaat acactttaat ttcagtcaaa aa 3452

<210> 124

<211> 1749

<212> DNA

<213>Homo sapiens

<400> 124

gtggcctcga ggtggtggca gggccgcccc ctgcagtccg gagacgaacg cacggaccgg 60

gcctccggag gcaggttcgg ctggaaggaa ccgctctcgc ttcgtcctac acttgcgcaa 120

atgtctccga gcttactcac atagcatatt ggtatatcaa aatgaaatgc aaggaaccaa 180

aaataacata attgaaggca gtaaaagtga aattaaatag gaagatcatc agtcaaggaa 240

gacccactgg agaggacaga aaatgaagca gtgttttatc atgtgtattt cagcaggtct 300

tcttgaaatt taactaaaaa tatgactgct ctctcttcag agaactgctc ttttcagtac 360

cagttacgtc aaacaaacca gcccctagac gttaactatc tgctattctt gatcatactt 420

gggaaaatat tattaaatat ccttacacta ggaatgagaa gaaaaaacac ctgtcaaaat 480

tttatggaat atttttgcat ttcactagca ttcgttgatc ttttactttt ggtaaacatt 540

tccattatat tgtatttcag ggattttgta cttttaagca ttaggttcac taaataccac 600

atctgcctat ttactcaaat tatttccttt acttatggct ttttgcatta tccagttttc 660

ctgacagctt gtatagatta ttgcctgaat ttctctaaaa caaccaagct ttcatttaag 720

tgtcaaaaat tattttattt ctttacagta attttaattt ggatttcagt ccttgcttat 780

gttttgggag acccagccat ctaccaaagc ctgaaggcac agaatgctta ttctcgtcac 840

tgtcctttct atgtcagcat tcagagttac tggctgtcat ttttcatggt gatgatttta 900

tttgtagctt tcataacctg ttgggaagaa gttactactt tggtacaggc tatcaggata 960

acttcctata tgaatgaaac tatcttatat tttccttttt catcccactc cagttatact 1020

gtgagatcta aaaaaatatt cttatccaag ctcattgtct gttttctcag tacctggtta 1080

ccatttgtac tacttcaggt aatcattgtt ttacttaaag ttcagattcc agcatatatt 1140

gagatgaata ttccctggtt atactttgtc aatagttttc tcattgctac agtgtattgg 1200

tttaattgtc acaagcttaa tttaaaagac attggattac ctttggatcc atttgtcaac 1260

tggaagtgct gcttcattcc acttacaatt cctaatcttg agcaaattga aaagcctata 1320

tcaataatga tttgttaata ttattaatta aaagttacag ctgtcataag atcataattt 1380

tatgaacaga aagaactcag gacatattaa aaaataaact gaactaaaac aacttttgcc 1440

ccctgactga tagcatttca gaatgtgtct tttgaagggc tataccagtt attaaatagt 1500

gttttatttt aaaaacaaaa taattccaag aagtttttat agttattcag ggacactata 1560

ttacaaatat tactttgtta ttaacacaaa aagtgataag agttaacatt tggctatact 1620

gatgtttgtg ttactcaaaa aaactactgg atgcaaactg ttatgtaaat ctgagatttc 1680

actgacaact ttaagatatc aacctaaaca tttttattaa atgttcaaat gtaagcaaga 1740

aaaaaaaaa 1749

<210> 125

<211> 2285

<212> DNA

<213>Homo sapiens

<400> 125

acccgccccc atctgcccaa gataatttta gtttccttgg gcctggaatc tggacacaca 60

gggctccccc ccgcctctga cttctctgtc cgaagtcggg acaccctcct accacctgta 120

gagaagcggg agtggatctg aaataaaatc caggaatctg ggggttccta gacggagcca 180

gacttcggaa cgggtgtcct gctactcctg ctggggctcc tccaggacaa gggcacacaa 240

ctggttccgt taagcccctc tctcgctcag acgccatgga gctggatctg tctccacctc 300

atcttagcag ctctccggaa gacctttgcc cagcccctgg gacccctcct gggactcccc 360

ggccccctga tacccctctg cctgaggagg taaagaggtc ccagcctctc ctcatcccaa 420

ccaccggcag gaaacttcga gaggaggaga ggcgtgccac ctccctcccc tctatcccca 480

accccttccc tgagctctgc agtcctccct cacagagccc aattctcggg ggcccctcca 540

gtgcaagggg gctgctcccc cgcgatgcca gccgccccca tgtagtaaag gtgtacagtg 600

aggatggggc ctgcaggtct gtggaggtgg cagcaggtgc cacagctcgc cacgtgtgtg 660

aaatgctggt gcagcgagct cacgccttga gcgacgagac ctgggggctg gtggagtgcc 720

acccccacct agcactggag cggggtttgg aggaccacga gtccgtggtg gaagtgcagg 780

ctgcctggcc cgtgggcgga gatagccgct tcgtcttccg gaaaaacttc gccaagtacg 840

aactgttcaa gagctcccca cactccctgt tcccagaaaa aatggtctcc agctgtctcg 900

atgcacacac tggtatatcc catgaagacc tcatccagaa cttcctgaat gctggcagct 960

ttcctgagat ccagggcttt ctgcagctgc ggggttcagg acggaagctt tggaaacgct 1020

ttttctgctt cttgcgccga tctggcctct attactccac caagggcacc tctaaggatc 1080

cgaggcacct gcagtacgtg gcagatgtga acgagtccaa cgtgtacgtg gtgacgcagg 1140

gccgcaagct ctacgggatg cccactgact tcggtttctg tgtcaagccc aacaagcttc 1200

gaaatggcca caaggggctt cggatcttct gcagtgaaga tgagcagagc cgcacctgct 1260

ggctggctgc cttccgcctc ttcaagtacg gggtgcagct gtacaagaat taccagcagg 1320

cacagtctcg ccatctgcat ccatcttgtt tgggctcccc acccttgaga agtgcctcag 1380

ataataccct ggtggccatg gacttctctg gccatgctgg gcgtgtcatt gagaaccccc 1440

gggaggctct gagtgtggcc ctggaggagg cccaggcctg gaggaagaag acaaaccacc 1500

gcctcagcct gcccatgcca gcctccggca cgagcctcag tgcagccatc caccgcaccc 1560

aactctggtt ccacgggcgc atttcccgtg aggagagcca gcggcttatt ggacagcagg 1620

gcttggtaga cggcctgttc ctggtccggg agagtcagcg gaacccccag ggctttgtcc 1680

tctctttgtg ccacctgcag aaagtgaagc attatctcat cctgccgagc gaggaggagg 1740

gccgcctgta cttcagcatg gatgatggcc agacccgctt cactgacctg ctgcagctcg 1800

tggagttcca ccagctgaac cgcggcatcc tgccgtgctt gctgcgccat tgctgcacgc 1860

gggtggccct ctgaccaggc cgtggactgg ctcatgcctc agcccgcctt caggctgccc 1920

gccgcccctc cacccatcca gtggactctg gggcgcggcc acaggggacg ggatgaggag 1980

cgggagggtt ccgccactcc agttttctcc tctgcttctt tgcctccctc agatagaaaa 2040

cagcccccac tccagtccac tcctgacccc tctcctcaag ggaaggcctt gggtggcccc 2100

ctctccttct cctagctctg gaggtgctgc tctagggcag ggaattatgg gagaagtggg 2160

ggcagcccag gcggtttcac gccccacact ttgtacagac cgagaggcca gttgatctgc 2220

tctgttttat actagtgaca ataaagatta ttttttgata caaaaaaaaa aaaaaaaaaa 2280

aaaaa 2285

<210> 126

<211> 935

<212> DNA

<213>Homo sapiens

<400> 126

agtcagaggt cgcgcaggcg ctggtacccc gttggtccgc gcgttgctgc gttgtgaggg 60

gtgtcagctc agtgcatccc aggcagctct tagtgtggag cagtgaactg tgtgtggttc 120

cttctacttg gggatcatgc agagagcttc acgtctgaag agagagctgc acatgttagc 180

cacagagcca cccccaggca tcacatgttg gcaagataaa gaccaaatgg atgacctgcg 240

agctcaaata ttaggtggag ccaacacacc ttatgagaaa ggtgttttta agctagaagt 300

tatcattcct gagaggtacc catttgaacc tcctcagatc cgatttctca ctccaattta 360

tcatccaaac attgattctg ctggaaggat ttgtctggat gttctcaaat tgccaccaaa 420

aggtgcttgg agaccatccc tcaacatcgc aactgtgttg acctctattc agctgctcat 480

gtcagaaccc aaccctgatg acccgctcat ggctgacata tcctcagaat ttaaatataa 540

taagccagcc ttcctcaaga atgccagaca gtggacagag aagcatgcaa gacagaaaca 600

aaaggctgat gaggaagaga tgcttgataa tctaccagag gctggtgact ccagagtaca 660

caactcaaca cagaaaagga aggccagtca gctagtaggc atagaaaaga aatttcatcc 720

tgatgtttag gggacttgtc ctggttcatc ttagttaatg tgttctttgc caaggtgatc 780

taagttgcct accttgaatt tttttttaaa tatatttgat gacataattt ttgtgtagtt 840

tatttatctt gtacatatgt attttgaaat cttttaaacc tgaaaaataa atagtcattt 900

aatgttgaaa aaaaaaaaaa aaaaaaaaaa aaaaa 935

<210> 127

<211> 2896

<212> DNA

<213>Homo sapiens

<400> 127

acgcttgcgc gcgggattta aactgcggcg gtttacgcgg cgttaagact tcgtagggtt 60

agcgaaattg aggtttcttg gtattgcgcg tttctcttcc ttgctgactc tccgaatggc 120

catggactcg tcgcttcagg cccgcctgtt tcccggtctc gctatcaaga tccaacgcag 180

taatggttta attcacagtg ccaatgtaag gactgtgaac ttggagaaat cctgtgtttc 240

agtggaatgg gcagaaggag gtgccacaaa gggcaaagag attgattttg atgatgtggc 300

tgcaataaac ccagaactct tacagcttct tcccttacat ccgaaggaca atctgccctt 360

gcaggaaaat gtaacaatcc agaaacaaaa acggagatcc gtcaactcca aaattcctgc 420

tccaaaagaa agtcttcgaa gccgctccac tcgcatgtcc actgtctcag agcttcgcat 480

cacggctcag gagaatgaca tggaggtgga gctgcctgca gctgcaaact cccgcaagca 540

gttttcagtt cctcctgccc ccactaggcc ttcctgccct gcagtggctg aaataccatt 600

gaggatggtc agcgaggaga tggaagagca agtccattcc atccgaggca gctcttctgc 660

aaaccctgtg aactcagttc ggaggaaatc atgtcttgtg aaggaagtgg aaaaaatgaa 720

gaacaagcga gaagagaaga aggcccagaa ctctgaaatg agaatgaaga gagctcagga 780

gtatgacagt agttttccaa actgggaatt tgcccgaatg attaaagaat ttcgggctac 840

tttggaatgt catccactta ctatgactga tcctatcgaa gagcacagaa tatgtgtctg 900

tgttaggaaa cgcccactga ataagcaaga attggccaag aaagaaattg atgtgatttc 960

cattcctagc aagtgtctcc tcttggtaca tgaacccaag ttgaaagtgg acttaacaaa 1020

gtatctggag aaccaagcat tctgctttga ctttgcattt gatgaaacag cttcgaatga 1080

agttgtctac aggttcacag caaggccact ggtacagaca atctttgaag gtggaaaagc 1140

aacttgtttt gcatatggcc agacaggaag tggcaagaca catactatgg gcggagacct 1200

ctctgggaaa gcccagaatg catccaaagg gatctatgcc atggcctccc gggacgtctt 1260

cctcctgaag aatcaaccct gctaccggaa gttgggcctg gaagtctatg tgacattctt 1320

cgagatctac aatgggaagc tgtttgacct gctcaacaag aaggccaagc tgcgcgtgct 1380

ggaggacggc aagcaacagg tgcaagtggt ggggctgcag gagcatctgg ttaactctgc 1440

tgatgatgtc atcaagatga tcgacatggg cagcgcctgc agaacctctg ggcagacatt 1500

tgccaactcc aattcctccc gctcccacgc gtgcttccaa attattcttc gagctaaagg 1560

gagaatgcat ggcaagttct ctttggtaga tctggcaggg aatgagcgag gcgcggacac 1620

ttccagtgct gaccggcaga cccgcatgga gggcgcagaa atcaacaaga gtctcttagc 1680

cctgaaggag tgcatcaggg ccctgggaca gaacaaggct cacaccccgt tccgtgagag 1740

caagctgaca caggtgctga gggactcctt cattggggag aactctagga cttgcatgat 1800

tgccacgatc tcaccaggca taagctcctg tgaatatact ttaaacaccc tgagatatgc 1860

agacagggtc aaggagctga gcccccacag tgggcccagt ggagagcagt tgattcaaat 1920

ggaaacagaa gagatggaag cctgctctaa cggggcgctg attccaggca atttatccaa 1980

ggaagaggag gaactgtctt cccagatgtc cagctttaac gaagccatga ctcagatcag 2040

ggagctggag gagaaggcta tggaagagct caaggagatc atacagcaag gaccagactg 2100

gcttgagctc tctgagatga ccgagcagcc agactatgac ctggagacct ttgtgaacaa 2160

agcggaatct gctctggccc agcaagccaa gcatttctca gccctgcgag atgtcatcaa 2220

ggccttgcgc ctggccatgc agctggaaga gcaggctagc agacaaataa gcagcaagaa 2280

acggccccag tgacgactgc aaataaaaat ctgtttggtt tgacacccag cctcttccct 2340

ggccctcccc agagaacttt gggtacctgg tgggtctagg cagggtctga gctgggacag 2400

gttctggtaa atgccaagta tgggggcatc tgggcccagg gcagctgggg agggggtcag 2460

agtgacatgg gacactcctt ttctgttcct cagttgtcgc cctcacgaga ggaaggagct 2520

cttagttacc cttttgtgtt gcccttcttt ccatcaaggg gaatgttctc agcatagagc 2580

tttctccgca gcatcctgcc tgcgtggact ggctgctaat ggagagctcc ctggggttgt 2640

cctggctctg gggagagaga cggagccttt agtacagcta tctgctggct ctaaaccttc 2700

tacgcctttg ggccgagcac tgaatgtctt gtactttaaa aaaatgtttc tgagacctct 2760

ttctacttta ctgtctccct agagatccta gaggatccct actgttttct gttttatgtg 2820

tttatacatt gtatgtaaca ataaagagaa aaaataaatc agctgtttaa gtgtgtggaa 2880

aaaaaaaaaa aaaaaa 2896

<210> 128

<211> 2209

<212> DNA

<213>Homo sapiens

<400> 128

actgcgcgcg tcgtgcgtaa tgacgtcagc gccggcggag aatttcaaat tcgaacggct 60

ttggcgggcc gaggaaggac ctggtgtttt gatgaccgct gtcctgtcta gcagatactt 120

gcacggttta cagaaattcg gtccctgggt cgtgtcagga aactggaaaa aaggtcataa 180

gcatgaagcg cagttcagtt tccagcggtg gtgctggccg cctctccatg caggagttaa 240

gatcccagga tgtaaataaa caaggcctct atacccctca aaccaaagag aaaccaacct 300

ttggaaagtt gagtataaac aaaccgacat ctgaaagaaa agtctcgcta tttggcaaaa 360

gaactagtgg acatggatcc cggaatagtc aacttggtat attttccagt tctgagaaaa 420

tcaaggaccc gagaccactt aatgacaaag cattcattca gcagtgtatt cgacaactct 480

gtgagtttct tacagaaaat ggttatgcac ataatgtgtc catgaaatct ctacaagctc 540

cctctgttaa agacttcctg aagatcttca catttcttta tggcttcctg tgcccctcat 600

acgaacttcc tgacacaaag tttgaagaag aggttccaag aatctttaaa gaccttgggt 660

atccttttgc actatccaaa agctccatgt acacagtggg ggctcctcat acatggcctc 720

acattgtggc agccttagtt tggctaatag actgcatcaa gatacatact gccatgaaag 780

aaagctcacc tttatttgat gatgggcagc cttggggaga agaaactgaa gatggaatta 840

tgcataataa gttgtttttg gactacacca taaaatgcta tgagagtttt atgagtggtg 900

ccgacagctt tgatgagatg aatgcagagc tgcagtcaaa actgaaggat ttatttaatg 960

tggatgcttt taagctggaa tcattagaag caaaaaacag agcattgaat gaacagattg 1020

caagattgga acaagaaaga gaaaaagaac cgaatcgtct agagtcgttg agaaaactga 1080

aggcttcctt acaaggagat gttcaaaagt atcaggcata catgagcaat ttggagtctc 1140

attcagccat tcttgaccag aaattaaatg gtctcaatga ggaaattgct agagtagaac 1200

tagaatgtga aacaataaaa caggagaaca ctcgactaca gaatatcatt gacaaccaga 1260

agtactcagt tgcagacatt gagcgaataa atcatgaaag aaatgaattg cagcagacta 1320

ttaataaatt aaccaaggac ctggaagctg aacaacagaa gttgtggaat gaggagttaa 1380

aatatgccag aggcaaagaa gcgattgaaa cacaattagc agagtatcac aaattggcta 1440

gaaaattaaa acttattcct aaaggtgctg agaattccaa aggttatgac tttgaaatta 1500

agtttaatcc cgaggctggt gccaactgcc ttgtcaaata cagggctcaa gtttatgtac 1560

ctcttaagga actcctgaat gaaactgaag aagaaattaa taaagcccta aataaaaaaa 1620

tgggtttgga ggatacttta gaacaattga atgcaatgat aacagaaagc aagagaagtg 1680

tgagaactct gaaagaagaa gttcaaaagc tggatgatct ttaccaacaa aaaattaagg 1740

aagcagagga agaggatgaa aaatgtgcca gtgagcttga gtccttggag aaacacaagc 1800

acctgctaga aagtactgtt aaccaggggc tcagtgaagc tatgaatgaa ttagatgctg 1860

ttcagcggga ataccaacta gttgtgcaaa ccacgactga agaaagacga aaagtgggaa 1920

ataacttgca acgtctgtta gagatggttg ctacacatgt tgggtctgta gagaaacatc 1980

ttgaggagca gattgctaaa gttgatagag aatatgaaga atgcatgtca gaagatctct 2040

cggaaaatat taaagagatt agagataagt atgagaagaa agctactcta attaagtctt 2100

ctgaagaatg aagataaaat gttgatcatg tatatatatc catagtgaat aaaattgtct 2160

cagtaaagtg taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2209

<210> 129

<211> 1740

<212> DNA

<213>Homo sapiens

<400> 129

ctccctcctc tgcaccatga ctacctgcag ccgccagttc acctcctcca gctccatgaa 60

gggctcctgc ggcatcgggg gcggcatcgg gggcggctcc agccgcatct cctccgtcct 120

ggccggaggg tcctgccgcg cccccagcac ctacgggggc ggcctgtctg tctcatcctc 180

ccgcttctcc tctgggggag cctatgggtt ggggggcggc tatggcggtg gcttcagcag 240

cagcagcagc agctttggta gtggctttgg gggaggatat ggtggtggcc ttggtgctgg 300

cttgggtggt ggctttggtg gtggctttgc tggtggtgat gggcttctgg tgggcagtga 360

gaaggtgacc atgcagaacc tcaacgaccg cctggcctcc tacctggaca aggtgcgtgc 420

tctggaggag gccaacgccg acctggaagt gaagatccgt gactggtacc agaggcagcg 480

gcctgctgag atcaaagact acagtcccta cttcaagacc attgaggacc tgaggaacaa 540

gattctcaca gccacagtgg acaatgccaa tgtccttctg cagattgaca atgcccgtct 600

ggccgcggat gacttccgca ccaagtatga gacagagttg aacctgcgca tgagtgtgga 660

agccgacatc aatggcctgc gcagggtgct ggacgaactg accctggcca gagctgacct 720

ggagatgcag attgagagcc tgaaggagga gctggcctac ctgaagaaga accacgagga 780

ggagatgaat gccctgagag gccaggtggg tggagatgtc aatgtggaga tggacgctgc 840

acctggcgtg gacctgagcc gcattctgaa cgagatgcgt gaccagtatg agaagatggc 900

agagaagaac cgcaaggatg ccgaggaatg gttcttcacc aagacagagg agctgaaccg 960

cgaggtggcc accaacagcg agctggtgca gagcggcaag agcgagatct cggagctccg 1020

gcgcaccatg cagaacctgg agattgagct gcagtcccag ctcagcatga aagcatccct 1080

ggagaacagc ctggaggaga ccaaaggtcg ctactgcatg cagctggccc agatccagga 1140

gatgattggc agcgtggagg agcagctggc ccagctccgc tgcgagatgg agcagcagaa 1200

ccaggagtac aagatcctgc tggacgtgaa gacgcggctg gagcaggaga tcgccaccta 1260

ccgccgcctg ctggagggcg aggacgccca cctctcctcc tcccagttct cctctggatc 1320

gcagtcatcc agagatgtga cctcctccag ccgccaaatc cgcaccaagg tcatggatgt 1380

gcacgatggc aaggtggtgt ccacccacga gcaggtcctt cgcaccaaga actgaggctg 1440

cccagccccg ctcaggccta ggaggccccc cgtgtggaca cagatcccac tggaagatcc 1500

cctctcctgc ccaagcactt cacagctgga ccctgcttca ccctcacccc ctcctggcaa 1560

tcaatacagc ttcattatct gagttgcata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1620

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1680

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740

<210> 130

<211> 2895

<212> DNA

<213>Homo sapiens

<400> 130

ctcttttgca ggggccgttc ctcggggcat gacgctggct cctgcacaga tcctgctcct 60

ctgtggcctt cctgggctgc cctcccctcc tccgggactg ctctggactg acactgctca 120

ggttcggatt ccctcaaaga ctttgggaga caagacttgg tccccctttt acaaacaagg 180

gaacggaggc tctagaactg acttcctgaa aggcttggat ccaaagctcc ctcagttcag 240

cggccacgtc tatttccctc agacacaggg atccttgaac ctgtgggctg tatctccccg 300

cggacttgga agaatcccaa gagagtgggg ctcccacagg ctggagtgca atggtgtgat 360

ctcggctcac tgcaacctcc acctcccagg ttcaagctat tctcctgcct cagcctcctg 420

agtagctggg attacagatc ctggtggctg tggtcggtaa ttccagcttc gtgctggcta 480

caggtggatg atgcccacct ggctgccgat gacctctgca ccaagtgagg ctgggtctct 540

ggagctgccc caggggctgg acaagctgac cctggccggg gccaacctgg agatgcagat 600

tgagaacctc aaggaggacc tggtctacct gaagaagaac cacaagcagg aaatgaacgt 660

cctttgaggt caggtggatg aggatgtcag tgtgaagatg gacactgtgc ctggagtgaa 720

cctgagctgc atcctgaatg agatgcgtga ccaggacaag acattggtgg agaagagctg 780

caaggatgcc gagggctggt tcttcagcat ggtgggtggc cgtgcgtaag caggtgtgta 840

cacgtgtggg cacatgtgct gcatgctggt gcagctggag cactggcaga tccacaggct 900

gtcccagttg gaaggacttt tggaaaccag ttggaccagc ccctcatgtt ttagatgtaa 960

aacgtgaggc tcagagagga ctcaagctca cacagccctt cactgtggcc tgcaaaatag 1020

atccaggtct ctacaagtct ggtcttgggt ttccaccaca gctgtttaca ggatgtgcgt 1080

atttgaatac atatgtatac ccttggcaag cacaggctga gtatctccgg tatcctaggg 1140

acagcaacag gcgcaaaaga ataacaccca gtgcctgtct ttgaggtgct gcagttcagt 1200

aggaaaaaga aatgcaaatg accgcagagc aggctgaatt cctccaagtt ccaatgtggg 1260

tgcagaggct ctctgtgtgc agaaagaggg gctgaactgc gaggtggcca ccaacacaga 1320

ggccctgcag agtggctgga tagagatatg gagctctacg tctctgtgca gaacctgagc 1380

cgtcccagct cagcaagaaa gcatcgctgg agggcagcct ggtggagatg gaggtgtgtt 1440

acaggaccct gccggcccag ctgcaggggc ttaacagaag catggagcag cagctgtgcg 1500

agctctgctg cgacacggag caccaggacc acaagcacag gtccttctgg acgtgaagac 1560

gtggctggag caggagatcg ccacctaccg ccgcttgctg gaggttgagg acgcccagag 1620

gtgatactga cgatgcaggc tggagtctgg ctgaggagcc ttgaatgcca agttaaagcg 1680

tctggactag atcacgtagg caatggggag ccatggaggg atttggagca ggagagtgaa 1740

atgaacatca agagatttta gaacattcac tctggctgca gagggagaaa tggatcagag 1800

gggtcagggc ggggccagag agatgtgtca gggggctgga gcagggagtc tggccagaga 1860

agtcccgtgc ggtggtgggt agtggggcag gggaaggaag gtggtgcacg cagaagagag 1920

gttatagctc aaaacagcgg gactggatgc ctggatctcg gggtaagcat ggctcacagt 1980

caggactcag taagtgtcgg gagaacacat gaaggagcag gcattgatgg ccctgggttt 2040

ctggttctga tgactgtgtg agtggtgaag agcaaggtgg gtggtggttg ggtttgcagt 2100

tgggaagggt gatcaggcct tcagctgaga gtgtcccgga gtctccatgc ttagtcacac 2160

gttgcagctt tttgctcccc ggaaatggtg aagtccatct atagtctaac aacagtctct 2220

cctgctttaa ttgggtctat ttgttgggcc ctctgggtta tggaaaaacc acttgctcag 2280

cttctccttg taaattcctg gtgagtagcc acagagtgcc gccagaccta ctgctgtgct 2340

gtttcttttt cttcttcctg ctgtgctgaa cccctgccct ttcattcttg ggcctgcgct 2400

aatttctgtg cattcccaac tgtgattttt caccaattta ggggaacctc ctctgccagg 2460

gcctacttct ccccagcagt gcttgcaggt gcctgggctg gctggcatcc ctgggctgat 2520

gggtgcttct ctccctgcag gctggccact cagtactcct tgtccctggc ctcgcagccc 2580

acccgggaag ccacagtgac cagccaccag gtgtgccatc gtggaggaag tccaggttgg 2640

agaggtggtc ttcttctgtg agcaggtcca cttctccacc cactgagacc cctttctgtc 2700

tgcgacagcc ccacctcgag ggccacggca cagccatcag ctccagctcc cagcatgcta 2760

ctgccacgcc ccgagtgtcc gtctgggccc cggtgcatgg cctgttgtct ttctgtatct 2820

actttctgca gcccctcact gaggaggcct cctgggtttg tccagtgcct actattaaag 2880

ctttgctcca agttc 2895

<210> 131

<211> 2529

<212> DNA

<213>Homo sapiens

<400> 131

gcatcctttt tgggctgctc acagccccca gcctctatgg tgaagacata cttgctagca 60

gcgtcaccaa cttgctgcca agagatcagt gctgcaaggc aaggttattt ctaactgagc 120

agagcctgcc aggaagaaag cgtttgcacc ccacaccact gtgcaggtgt gaccggtgag 180

ctcacagctg ccccccaggc atgcccagcc cacttaatca ttcacagctc gacagctctc 240

tcgcccagcc cagttctgga agggataaaa agggggcatc accgttcctg ggtaacagag 300

ccaccttctg cgtcctgctg agctctgttc tctccagcac ctcccaaccc actagtgcct 360

ggttctcttg ctccaccagg aacaagccac catgtctcgc cagtcaagtg tgtccttccg 420

gagcgggggc agtcgtagct tcagcaccgc ctctgccatc accccgtctg tctcccgcac 480

cagcttcacc tccgtgtccc ggtccggggg tggcggtggt ggtggcttcg gcagggtcag 540

ccttgcgggt gcttgtggag tgggtggcta tggcagccgg agcctctaca acctgggggg 600

ctccaagagg atatccatca gcactagagg aggcagcttc aggaaccggt ttggtgctgg 660

tgctggaggc ggctatggct ttggaggtgg tgccggtagt ggatttggtt tcggcggtgg 720

agctggtggt ggctttgggc tcggtggcgg agctggcttt ggaggtggct tcggtggccc 780

tggctttcct gtctgccctc ctggaggtat ccaagaggtc actgtcaacc agagtctcct 840

gactcccctc aacctgcaaa tcgaccccag catccagagg gtgaggaccg aggagcgcga 900

gcagatcaag accctcaaca ataagtttgc ctccttcatc gacaaggtgc ggttcctgga 960

gcagcagaac aaggttctgg acaccaagtg gaccctgctg caggagcagg gcaccaagac 1020

tgtgaggcag aacctggagc cgttgttcga gcagtacatc aacaacctca ggaggcagct 1080

ggacagcatc gtgggggaac ggggccgcct ggactcagag ctgagaaaca tgcaggacct 1140

ggtggaagac ttcaagaaca agtatgagga tgaaatcaac aagcgtacca ctgctgagaa 1200

tgagtttgtg atgctgaaga aggatgtaga tgctgcctac atgaacaagg tggagctgga 1260

ggccaaggtt gatgcactga tggatgagat taacttcatg aagatgttct ttgatgcgga 1320

gctgtcccag atgcagacgc atgtctctga cacctcagtg gtcctctcca tggacaacaa 1380

ccgcaacctg gacctggata gcatcatcgc tgaggtcaag gcccagtatg aggagattgc 1440

caaccgcagc cggacagaag ccgagtcctg gtatcagacc aagtatgagg agctgcagca 1500

gacagctggc cggcatggcg atgacctccg caacaccaag catgagatca cagagatgaa 1560

ccggatgatc cagaggctga gagccgagat tgacaatgtc aagaaacagt gcgccaatct 1620

gcagaacgcc attgcggatg ccgagcagcg tggggagctg gccctcaagg atgccaggaa 1680

caagctggcc gagctggagg aggccctgca gaaggccaag caggacatgg cccggctgct 1740

gcgtgagtac caggagctca tgaacaccaa gctggccctg gacgtggaga tcgccactta 1800

ccgcaagctg ctggagggcg aggaatgcag actcagtgga gaaggagttg gaccagtcaa 1860

catctctgtt gtcacaagca gtgtttcctc tggatatggc agtggcagtg gctatggcgg 1920

tggcctcggt ggaggtcttg gcggcggcct cggtggaggt cttgccggag gtagcagtgg 1980

aagctactac tccagcagca gtgggggtgt cggcctaggt ggtgggctca gtgtgggggg 2040

ctctggcttc agtgcaagca gtggccgagg gctgggggtg ggctttggca gtggcggggg 2100

tagcagctcc agcgtcaaat ttgtctccac cacctcctcc tcccggaaga gcttcaagag 2160

ctaagaacct gctgcaagtc actgccttcc aagtgcagca acccagccca tggagattgc 2220

ctcttctagg cagttgctca agccatgttt tatccttttc tggagagtag tctagaccaa 2280

gccaattgca gaaccacatt ctttggttcc caggagagcc ccattcccag cccctggtct 2340

cccgtgccgc agttctatat tctgcttcaa atcagccttc aggtttccca cagcatggcc 2400

cctgctgaca cgagaaccca aagttttccc aaatctaaat catcaaaaca gaatccccac 2460

cccaatccca aattttgttt tggttctaac tacctccaga atgtgttcaa taaaatgctt 2520

ttataatat 2529

<210> 132

<211> 6816

<212> DNA

<213>Homo sapiens

<400> 132

ggacggccga gcggcagggc gctcgcgcgc gcccactagt ggccggagga gaaggctccc 60

gcggaggccg cgctgcccgc cccctcccct ggggaggctc gcgttcccgc tgctcgcgcc 120

tgcgccgccc gccggcctca ggaacgcgcc ctcttcgccg gcgcgcgccc tcgcagtcac 180

cgccacccac cagctccggc accaacagca gcgccgctgc caccgcccac cttctgccgc 240

cgccaccaca gccaccttct cctcctccgc tgtcctctcc cgtcctcgcc tctgtcgact 300

atcaggtgaa ctttgaacca ggatggctga gccccgccag gagttcgaag tgatggaaga 360

tcacgctggg acgtacgggt tgggggacag gaaagatcag gggggctaca ccatgcacca 420

agaccaagag ggtgacacgg acgctggcct gaaagaatct cccctgcaga cccccactga 480

ggacggatct gaggaaccgg gctctgaaac ctctgatgct aagagcactc caacagcgga 540

agatgtgaca gcacccttag tggatgaggg agctcccggc aagcaggctg ccgcgcagcc 600

ccacacggag atcccagaag gaaccacagc tgaagaagca ggcattggag acacccccag 660

cctggaagac gaagctgctg gtcacgtgac ccaagagcct gaaagtggta aggtggtcca 720

ggaaggcttc ctccgagagc caggcccccc aggtctgagc caccagctca tgtccggcat 780

gcctggggct cccctcctgc ctgagggccc cagagaggcc acacgccaac cttcggggac 840

aggacctgag gacacagagg gcggccgcca cgcccctgag ctgctcaagc accagcttct 900

aggagacctg caccaggagg ggccgccgct gaagggggca gggggcaaag agaggccggg 960

gagcaaggag gaggtggatg aagaccgcga cgtcgatgag tcctcccccc aagactcccc 1020

tccctccaag gcctccccag cccaagatgg gcggcctccc cagacagccg ccagagaagc 1080

caccagcatc ccaggcttcc cagcggaggg tgccatcccc ctccctgtgg atttcctctc 1140

caaagtttcc acagagatcc cagcctcaga gcccgacggg cccagtgtag ggcgggccaa 1200

agggcaggat gcccccctgg agttcacgtt tcacgtggaa atcacaccca acgtgcagaa 1260

ggagcaggcg cactcggagg agcatttggg aagggctgca tttccagggg cccctggaga 1320

ggggccagag gcccggggcc cctctttggg agaggacaca aaagaggctg accttccaga 1380

gccctctgaa aagcagcctg ctgctgctcc gcgggggaag cccgtcagcc gggtccctca 1440

actcaaagct cgcatggtca gtaaaagcaa agacgggact ggaagcgatg acaaaaaagc 1500

caagacatcc acacgttcct ctgctaaaac cttgaaaaat aggccttgcc ttagccccaa 1560

acaccccact cctggtagct cagaccctct gatccaaccc tccagccctg ctgtgtgccc 1620

agagccacct tcctctccta aatacgtctc ttctgtcact tcccgaactg gcagttctgg 1680

agcaaaggag atgaaactca agggggctga tggtaaaacg aagatcgcca caccgcgggg 1740

agcagcccct ccaggccaga agggccaggc caacgccacc aggattccag caaaaacccc 1800

gcccgctcca aagacaccac ccagctctgc gactaagcaa gtccagagaa gaccaccccc 1860

tgcagggccc agatctgaga gaggtgaacc tccaaaatca ggggatcgca gcggctacag 1920

cagccccggc tccccaggca ctcccggcag ccgctcccgc accccgtccc ttccaacccc 1980

acccacccgg gagcccaaga aggtggcagt ggtccgtact ccacccaagt cgccgtcttc 2040

cgccaagagc cgcctgcaga cagcccccgt gcccatgcca gacctgaaga atgtcaagtc 2100

caagatcggc tccactgaga acctgaagca ccagccggga ggcgggaagg tgcagataat 2160

taataagaag ctggatctta gcaacgtcca gtccaagtgt ggctcaaagg ataatatcaa 2220

acacgtcccg ggaggcggca gtgtgcaaat agtctacaaa ccagttgacc tgagcaaggt 2280

gacctccaag tgtggctcat taggcaacat ccatcataaa ccaggaggtg gccaggtgga 2340

agtaaaatct gagaagcttg acttcaagga cagagtccag tcgaagattg ggtccctgga 2400

caatatcacc cacgtccctg gcggaggaaa taaaaagatt gaaacccaca agctgacctt 2460

ccgcgagaac gccaaagcca agacagacca cggggcggag atcgtgtaca agtcgccagt 2520

ggtgtctggg gacacgtctc cacggcatct cagcaatgtc tcctccaccg gcagcatcga 2580

catggtagac tcgccccagc tcgccacgct agctgacgag gtgtctgcct ccctggccaa 2640

gcagggtttg tgatcaggcc cctggggcgg tcaataattg tggagaggag agaatgagag 2700

agtgtggaaa aaaaaagaat aatgacccgg cccccgccct ctgcccccag ctgctcctcg 2760

cagttcggtt aattggttaa tcacttaacc tgcttttgtc actcggcttt ggctcgggac 2820

ttcaaaatca gtgatgggag taagagcaaa tttcatcttt ccaaattgat gggtgggcta 2880

gtaataaaat atttaaaaaa aaacattcaa aaacatggcc acatccaaca tttcctcagg 2940

caattccttt tgattctttt ttcttccccc tccatgtaga agagggagaa ggagaggctc 3000

tgaaagctgc ttctggggga tttcaaggga ctgggggtgc caaccacctc tggccctgtt 3060

gtgggggtgt cacagaggca gtggcagcaa caaaggattt gaaacttggt gtgttcgtgg 3120

agccacaggc agacgatgtc aaccttgtgt gagtgtgacg ggggttgggg tggggcggga 3180

ggccacgggg gaggccgagg caggggctgg gcagagggga gaggaagcac aagaagtggg 3240

agtgggagag gaagccacgt gctggagagt agacatcccc ctccttgccg ctgggagagc 3300

caaggcctat gccacctgca gcgtctgagc ggccgcctgt ccttggtggc cgggggtggg 3360

ggcctgctgt gggtcagtgt gccaccctct gcagggcagc ctgtgggaga agggacagcg 3420

ggtaaaaaga gaaggcaagc tggcaggagg gtggcacttc gtggatgacc tccttagaaa 3480

agactgacct tgatgtcttg agagcgctgg cctcttcctc cctccctgca gggtaggggg 3540

cctgagttga ggggcttccc tctgctccac agaaaccctg ttttattgag ttctgaaggt 3600

tggaactgct gccatgattt tggccacttt gcagacctgg gactttaggg ctaaccagtt 3660

ctctttgtaa ggacttgtgc ctcttgggag acgtccaccc gtttccaagc ctgggccact 3720

ggcatctctg gagtgtgtgg gggtctggga ggcaggtccc gagccccctg tccttcccac 3780

ggccactgca gtcaccccgt ctgcgccgct gtgctgttgt ctgccgtgag agcccaatca 3840

ctgcctatac ccctcatcac acgtcacaat gtcccgaatt cccagcctca ccaccccttc 3900

tcagtaatga ccctggttgg ttgcaggagg tacctactcc atactgaggg tgaaattaag 3960

ggaaggcaaa gtccaggcac aagagtggga ccccagcctc tcactctcag ttccactcat 4020

ccaactggga ccctcaccac gaatctcatg atctgattcg gttccctgtc tcctcctccc 4080

gtcacagatg tgagccaggg cactgctcag ctgtgaccct aggtgtttct gccttgttga 4140

catggagaga gccctttccc ctgagaaggc ctggcccctt cctgtgctga gcccacagca 4200

gcaggctggg tgtcttggtt gtcagtggtg gcaccaggat ggaagggcaa ggcacccagg 4260

gcaggcccac agtcccgctg tcccccactt gcaccctagc ttgtagctgc caacctccca 4320

gacagcccag cccgctgctc agctccacat gcatagtatc agccctccac acccgacaaa 4380

ggggaacaca cccccttgga aatggttctt ttcccccagt cccagctgga agccatgctg 4440

tctgttctgc tggagcagct gaacatatac atagatgttg ccctgccctc cccatctgca 4500

ccctgttgag ttgtagttgg atttgtctgt ttatgcttgg attcaccaga gtgactatga 4560

tagtgaaaag aaaaaaaaaa aaaaaaaagg acgcatgtat cttgaaatgc ttgtaaagag 4620

gtttctaacc caccctcacg aggtgtctct cacccccaca ctgggactcg tgtggcctgt 4680

gtggtgccac cctgctgggg cctcccaagt tttgaaaggc tttcctcagc acctgggacc 4740

caacagagac cagcttctag cagctaagga ggccgttcag ctgtgacgaa ggcctgaagc 4800

acaggattag gactgaagcg atgatgtccc cttccctact tccccttggg gctccctgtg 4860

tcagggcaca gactaggtct tgtggctggt ctggcttgcg gcgcgaggat ggttctctct 4920

ggtcatagcc cgaagtctca tggcagtccc aaaggaggct tacaactcct gcatcacaag 4980

aaaaaggaag ccactgccag ctggggggat ctgcagctcc cagaagctcc gtgagcctca 5040

gccacccctc agactgggtt cctctccaag ctcgccctct ggaggggcag cgcagcctcc 5100

caccaagggc cctgcgacca cagcagggat tgggatgaat tgcctgtcct ggatctgctc 5160

tagaggccca agctgcctgc ctgaggaagg atgacttgac aagtcaggag acactgttcc 5220

caaagccttg accagagcac ctcagcccgc tgaccttgca caaactccat ctgctgccat 5280

gagaaaaggg aagccgcctt tgcaaaacat tgctgcctaa agaaactcag cagcctcagg 5340

cccaattctg ccacttctgg tttgggtaca gttaaaggca accctgaggg acttggcagt 5400

agaaatccag ggcctcccct ggggctggca gcttcgtgtg cagctagagc tttacctgaa 5460

aggaagtctc tgggcccaga actctccacc aagagcctcc ctgccgttcg ctgagtccca 5520

gcaattctcc taagttgaag ggatctgaga aggagaagga aatgtggggt agatttggtg 5580

gtggttagag atatgccccc ctcattactg ccaacagttt cggctgcatt tcttcacgca 5640

cctcggttcc tcttcctgaa gttcttgtgc cctgctcttc agcaccatgg gccttcttat 5700

acggaaggct ctgggatctc ccccttgtgg ggcaggctct tggggccagc ctaagatcat 5760

ggtttagggt gatcagtgct ggcagataaa ttgaaaaggc acgctggctt gtgatcttaa 5820

atgaggacaa tccccccagg gctgggcact cctcccctcc cctcacttct cccacctgca 5880

gagccagtgt ccttgggtgg gctagatagg atatactgta tgccggctcc ttcaagctgc 5940

tgactcactt tatcaatagt tccatttaaa ttgacttcag tggtgagact gtatcctgtt 6000

tgctattgct tgttgtgcta tggggggagg ggggaggaat gtgtaagata gttaacatgg 6060

gcaaagggag atcttggggt gcagcactta aactgcctcg taaccctttt catgatttca 6120

accacatttg ctagagggag ggagcagcca cggagttaga ggcccttggg gtttctcttt 6180

tccactgaca ggctttccca ggcagctggc tagttcattc cctccccagc caggtgcagg 6240

cgtaggaata tggacatctg gttgctttgg cctgctgccc tctttcaggg gtcctaagcc 6300

cacaatcatg cctccctaag accttggcat ccttccctct aagccgttgg cacctctgtg 6360

ccacctctca cactggctcc agacacacag cctgtgcttt tggagctgag atcactcgct 6420

tcaccctcct catctttgtt ctccaagtaa agccacgagg tcggggcgag ggcagaggtg 6480

atcacctgcg tgtcccatct acagacctgc agcttcataa aacttctgat ttctcttcag 6540

ctttgaaaag ggttaccctg ggcactggcc tagagcctca cctcctaata gacttagccc 6600

catgagtttg ccatgttgag caggactatt tctggcactt gcaagtccca tgatttcttc 6660

ggtaattctg agggtggggg gagggacatg aaatcatctt agcttagctt tctgtctgtg 6720

aatgtctata tagtgtattg tgtgttttaa caaatgattt acactgactg ttgctgtaaa 6780

agtgaatttg gaaataaagt tattactctg attaaa 6816

<210> 133

<211> 2372

<212> DNA

<213>Homo sapiens

<400> 133

gcaccgcgcg agcttggctg cttctggggc ctgtgtggcc ctgtgtgtcg gaaagatgga 60

gcaagaagcc gagcccgagg ggcggccgcg acccctctga ccgagatcct gctgctttcg 120

cagccaggag caccgtccct ccccggatta gtgcgtacga gcgcccagtg ccctggcccg 180

gagagtggaa tgatccccga ggcccagggc gtcgtgcttc cgcagtagtc agtccccgtg 240

aaggaaactg gggagtcttg agggaccccc gactccaagc gcgaaaaccc cggatggtga 300

ggagcaggca aatgtgcaat accaacatgt ctgtacctac tgatggtgct gtaaccacct 360

cacagattcc agcttcggaa caagagaccc tggttagacc aaagccattg cttttgaagt 420

tattaaagtc tgttggtgca caaaaagaca cttatactat gaaagaggtt cttttttatc 480

ttggccagta tattatgact aaacgattat atgatgagaa gcaacaacat attgtatatt 540

gttcaaatga tcttctagga gatttgtttg gcgtgccaag cttctctgtg aaagagcaca 600

ggaaaatata taccatgatc tacaggaact tggtagtagt caatcagcag gaatcatcgg 660

actcaggtac atctgtgagt gagaacaggt gtcaccttga aggtgggagt gatcaaaagg 720

accttgtaca agagcttcag gaagagaaac cttcatcttc acatttggtt tctagaccat 780

ctacctcatc tagaaggaga gcaattagtg agacagaaga aaattcagat gaattatctg 840

gtgaacgaca aagaaaacgc cacaaatctg atagtatttc cctttccttt gatgaaagcc 900

tggctctgtg tgtaataagg gagatatgtt gtgaaagaag cagtagcagt gaatctacag 960

ggacgccatc gaatccggat cttgatgctg gtgtaagtga acattcaggt gattggttgg 1020

atcaggattc agtttcagat cagtttagtg tagaatttga agttgaatct ctcgactcag 1080

aagattatag ccttagtgaa gaaggacaag aactctcaga tgaagatgat gaggtatatc 1140

aagttactgt gtatcaggca ggggagagtg atacagattc atttgaagaa gatcctgaaa 1200

tttccttagc tgactattgg aaatgcactt catgcaatga aatgaatccc ccccttccat 1260

cacattgcaa cagatgttgg gcccttcgtg agaattggct tcctgaagat aaagggaaag 1320

ataaagggga aatctctgag aaagccaaac tggaaaactc aacacaagct gaagagggct 1380

ttgatgttcc tgattgtaaa aaaactatag tgaatgattc cagagagtca tgtgttgagg 1440

aaaatgatga taaaattaca caagcttcac aatcacaaga aagtgaagac tattctcagc 1500

catcaacttc tagtagcatt atttatagca gccaagaaga tgtgaaagag tttgaaaggg 1560

aagaaaccca agacaaagaa gagagtgtgg aatctagttt gccccttaat gccattgaac 1620

cttgtgtgat ttgtcaaggt cgacctaaaa atggttgcat tgtccatggc aaaacaggac 1680

atcttatggc ctgctttaca tgtgcaaaga agctaaagaa aaggaataag ccctgcccag 1740

tatgtagaca accaattcaa atgattgtgc taacttattt cccctagttg acctgtctat 1800

aagagaatta tatatttcta actatataac cctaggaatt tagacaacct gaaatttatt 1860

cacatatatc aaagtgagaa aatgcctcaa ttcacataga tttcttctct ttagtataat 1920

tgacctactt tggtagtgga atagtgaata cttactataa tttgacttga atatgtagct 1980

catcctttac accaactcct aattttaaat aatttctact ctgtcttaaa tgagaagtac 2040

ttggtttttt ttttcttaaa tatgtatatg acatttaaat gtaacttatt attttttttg 2100

agaccgagtc ttgctctgtt acccaggctg gagtgcagtg ggtgatcttg gctcactgca 2160

agctctgccc tccccgggtt cgcaccattc tcctgcctca gcctcccaat tagcttggcc 2220

tacagtcatc tgccaccaca cctggctaat tttttgtact tttagtagag acagggtttc 2280

accgtgttag ccaggatggt ctcgatctcc tgacctcgtg atccgcccac ctcggcctcc 2340

caaagtgctg ggattacagg catgagccac cg 2372

<210> 134

<211> 2486

<212> DNA

<213>Homo sapiens

<400> 134

gagatttgat tcccttggcg ggcggaagcg gccacaaccc ggcgatcgaa aagattctta 60

ggaacgccgt accagccgcg tctctcagga cagcaggccc ctgtccttct gtcgggcgcc 120

gctcagccgt gccctccgcc cctcaggttc tttttctaat tccaaataaa cttgcaagag 180

gactatgaaa gattatgatg aacttctcaa atattatgaa ttacatgaaa ctattgggac 240

aggtggcttt gcaaaggtca aacttgcctg ccatatcctt actggagaga tggtagctat 300

aaaaatcatg gataaaaaca cactagggag tgatttgccc cggatcaaaa cggagattga 360

ggccttgaag aacctgagac atcagcatat atgtcaactc taccatgtgc tagagacagc 420

caacaaaata ttcatggttc ttgagtactg ccctggagga gagctgtttg actatataat 480

ttcccaggat cgcctgtcag aagaggagac ccgggttgtc ttccgtcaga tagtatctgc 540

tgttgcttat gtgcacagcc agggctatgc tcacagggac ctcaagccag aaaatttgct 600

gtttgatgaa tatcataaat taaagctgat tgactttggt ctctgtgcaa aacccaaggg 660

taacaaggat taccatctac agacatgctg tgggagtctg gcttatgcag cacctgagtt 720

aatacaaggc aaatcatatc ttggatcaga ggcagatgtt tggagcatgg gcatactgtt 780

atatgttctt atgtgtggat ttctaccatt tgatgatgat aatgtaatgg ctttatacaa 840

gaagattatg agaggaaaat atgatgttcc caagtggctc tctcccagta gcattctgct 900

tcttcaacaa atgctgcagg tggacccaaa gaaacggatt tctatgaaaa atctattgaa 960

ccatccctgg atcatgcaag attacaacta tcctgttgag tggcaaagca agaatccttt 1020

tattcacctc gatgatgatt gcgtaacaga actttctgta catcacagaa acaacaggca 1080

aacaatggag gatttaattt cactgtggca gtatgatcac ctcacggcta cctatcttct 1140

gcttctagcc aagaaggctc ggggaaaacc agttcgttta aggctttctt ctttctcctg 1200

tggacaagcc agtgctaccc cattcacaga catcaagtca aataattgga gtctggaaga 1260

tgtgaccgca agtgataaaa attatgtggc gggattaata gactatgatt ggtgtgaaga 1320

tgatttatca acaggtgctg ctactccccg aacatcacag tttaccaagt actggacaga 1380

atcaaatggg gtggaatcta aatcattaac tccagcctta tgcagaacac ctgcaaataa 1440

attaaagaac aaagaaaatg tatatactcc taagtctgct gtaaagaatg aagagtactt 1500

tatgtttcct gagccaaaga ctccagttaa taagaaccag cataagagag aaatactcac 1560

tacgccaaat cgttacacta caccctcaaa agctagaaac cagtgcctga aagaaactcc 1620

aattaaaata ccagtaaatt caacaggaac agacaagtta atgacaggtg tcattagccc 1680

tgagaggcgg tgccgctcag tggaattgga tctcaaccaa gcacatatgg aggagactcc 1740

aaaaagaaag ggagccaaag tgtttgggag ccttgaaagg gggttggata aggttatcac 1800

tgtgctcacc aggagcaaaa ggaagggttc tgccagagac gggcccagaa gactaaagct 1860

tcactataac gtgactacaa ctagattagt gaatccagat caactgttga atgaaataat 1920

gtctattctt ccaaagaagc atgttgactt tgtacaaaag ggttatacac tgaagtgtca 1980

aacacagtca gattttggga aagtgacaat gcaatttgaa ttagaagtgt gccagcttca 2040

aaaacccgat gtggtgggta tcaggaggca gcggcttaag ggcgatgcct gggtttacaa 2100

aagattagtg gaagacatcc tatctagctg caaggtataa ttgatggatt cttccatcct 2160

gccggatgag tgtgggtgtg atacagccta cataaagact gttatgatcg ctttgatttt 2220

aaagttcatt ggaactacca acttgtttct aaagagctat cttaagacca atatctcttt 2280

gtttttaaac aaaagatatt attttgtgta tgaatctaaa tcaagcccat ctgtcattat 2340

gttactgtct tttttaatca tgtggttttg tatattaata attgttgact ttcttagatt 2400

cacttccata tgtgaatgta agctcttaac tatgtctctt tgtaatgtgt aatttctttc 2460

tgaaataaaa ccatttgtga atatag 2486

<210> 135

<211> 1140

<212> DNA

<213>Homo sapiens

<220>

<221>Miscellaneous feature

<222> (1140)..(1140)

<223>N is a, c, g or t

<400> 135

gcagcggagg agcccagtcc acgatggccc ggtccctggt gtgccttggt gtcatcatct 60

tgctgtctgc cttctccgga cctggtgtca ggggtggtcc tatgcccaag ctggctgacc 120

ggaagctgtg tgcggaccag gagtgcagcc accctatctc catggctgtg gcccttcagg 180

actacatggc ccccgactgc cgattcctga ccattcaccg gggccaagtg gtgtatgtct 240

tctccaagct gaagggccgt gggcggctct tctggggagg cagcgttcag ggagattact 300

atggagatct ggctgctcgc ctgggctatt tccccagtag cattgtccga gaggaccaga 360

ccctgaaacc tggcaaagtc gatgtgaaga cagacaaatg ggatttctac tgccagtgag 420

ctcagcctac cgctggccct gccgtttccc ctccttgggt ttatgcaaat acaatcagcc 480

cagtgcaaaa aaaaaaaaaa aaaaaaaaaa cttcggagaa gagatagcaa caaaaggccg 540

cttgtgtgaa ggcgccaaaa gttttcgccc aagagacctt cggcctcccc cagggcgcgc 600

gcaaaggcgc cttgttttga caacctcttg gacaaccgga ggggctaccg cccggagacc 660

cctgtggtgg accccccggg caacccggtg tgacagggta ctcaccccca cggctttgtc 720

gggggtccca ccaaaggccc caaagaggct ctttcaaggc actattcctt gttgtagacc 780

ttgtgtgtgc cacaggcgcc aaagaaacct cggggggcta acaaacgcac gtgcttggca 840

gctccgagaa ggctctctcc cacccgaggg gtggacgcaa cagggggaat gggccatcat 900

attgttgccc ccggtgggca ccaactcttt ttcccccata gagaggcctt agcacactat 960

gtggggcacg ttattgccgc ctagagaaac cgagcgccag aaaatttcga aggggggggc 1020

gcttctcatc attttgcgca aaaccccctt gtgggagtat gccccgaact cctctggaac 1080

acacaagcga cacttgcgcg gggtctgcaa aaaacctcct gttgggaagc cggcttcacn 1140

<210> 136

<211> 12507

<212> DNA

<213>Homo sapiens

<400> 136

taccgggcgg aggtgagcgc ggcgccggct cctcctgcgg cggactttgg gtgcgacttg 60

acgagcggtg gttcgacaag tggccttgcg ggccggatcg tcccagtgga agagttgtaa 120

atttgcttct ggccttcccc tacggattat acctggcctt cccctacgga ttatactcaa 180

cttactgttt agaaaatgtg gcccacgaga cgcctggtta ctatcaaaag gagcggggtc 240

gacggtcccc actttcccct gagcctcagc acctgcttgt ttggaagggg tattgaatgt 300

gacatccgta tccagcttcc tgttgtgtca aaacaacatt gcaaaattga aatccatgag 360

caggaggcaa tattacataa tttcagttcc acaaatccaa cacaagtaaa tgggtctgtt 420

attgatgagc ctgtacggct aaaacatgga gatgtaataa ctattattga tcgttccttc 480

aggtatgaaa atgaaagtct tcagaatgga aggaagtcaa ctgaatttcc aagaaaaata 540

cgtgaacagg agccagcacg tcgtgtctca agatctagct tctcttctga ccctgatgag 600

aaagctcaag attccaaggc ctattcaaaa atcactgaag gaaaagtttc aggaaatcct 660

caggtacata tcaagaatgt caaagaagac agtaccgcag atgactcaaa agacagtgtt 720

gctcagggaa caactaatgt tcattcctca gaacatgctg gacgtaatgg cagaaatgca 780

gctgatccca tttctgggga ttttaaagaa atttccagcg ttaaattagt gagccgttat 840

ggagaattga agtctgttcc cactacacaa tgtcttgaca atagcaaaaa aaatgaatct 900

cccttttgga agctttatga gtcagtgaag aaagagttgg atgtaaaatc acaaaaagaa 960

aatgtcctac agtattgtag aaaatctgga ttacaaactg attacgcaac agagaaagaa 1020

agtgctgatg gtttacaggg ggagacccaa ctgttggtct cgcgtaagtc aagaccaaaa 1080

tctggtggga gcggccacgc tgtggcagag cctgcttcac ctgaacaaga gcttgaccag 1140

aacaagggga agggaagaga cgtggagtct gttcagactc ccagcaaggc tgtgggcgcc 1200

agctttcctc tctatgagcc ggctaaaatg aagacccctg tacaatattc acagcaacaa 1260

aattctccac aaaaacataa gaacaaagac ctgtatacta ctggtagaag agaatctgtg 1320

aatctgggta aaagtgaagg cttcaaggct ggtgataaaa ctcttactcc caggaagctt 1380

tcaactagaa atcgaacacc agctaaagtt gaagatgcag ctgactctgc cactaagcca 1440

gaaaatctct cttccaaaac cagaggaagt attcctacag atgtggaagt tctgcctacg 1500

gaaactgaaa ttcacaatga gccattttta actctgtggc tcactcaagt tgagaggaag 1560

atccaaaagg attccctcag caagcctgag aaattgggca ctacagctgg acagatgtgc 1620

tctgggttac ctggtcttag ttcagttgat atcaacaact ttggtgattc cattaatgag 1680

agtgagggaa tacctttgaa aagaaggcgt gtgtcctttg gtgggcacct aagacctgaa 1740

ctatttgatg aaaacttgcc tcctaatacg cctctcaaaa ggggagaagc cccaaccaaa 1800

agaaagtctc tggtaatgca cactccacct gtcctgaaga aaatcatcaa ggaacagcct 1860

caaccatcag gaaaacaaga gtcaggttca gaaatccatg tggaagtgaa ggcacaaagc 1920

ttggttataa gccctccagc tcctagtcct aggaaaactc cagttgccag tgatcaacgc 1980

cgtaggtcct gcaaaacagc ccctgcttcc agcagcaaat ctcagacaga ggttcctaag 2040

agaggaggga gaaagagtgg caacctgcct tcaaagagag tgtctatcag ccgaagtcaa 2100

catgatattt tacagatgat atgttccaaa agaagaagtg gtgcttcgga agcaaatctg 2160

attgttgcaa aatcatgggc agatgtagta aaacttggtg caaaacaaac acaaactaaa 2220

gtcataaaac atggtcctca aaggtcaatg aacaaaaggc aaagaagacc tgctactcca 2280

aagaagcctg tgggcgaagt tcacagtcaa tttagtacag gccacgcaaa ctctccttgt 2340

accataataa tagggaaagc tcatactgaa aaagtacatg tgcctgctcg accctacaga 2400

gtgctcaaca acttcatttc caaccaaaaa atggacttta aggaagatct ttcaggaata 2460

gctgaaatgt tcaagacccc agtgaaggag caaccgcagt tgacaagcac atgtcacatc 2520

gctatttcaa attcagagaa tttgcttgga aaacagtttc aaggaactga ttcaggagaa 2580

gaacctctgc tccccacctc agagagtttt ggaggaaatg tgttcttcag tgcacagaat 2640

gcagcaaaac agccatctga taaatgctct gcaagccctc ccttaagacg gcagtgtatt 2700

agagaaaatg gaaacgtagc aaaaacgccc aggaacacct acaaaatgac ttctctggag 2760

acaaaaactt cagatactga gacagagcct tcaaaaacag tatccactgc aaacaggtca 2820

ggaaggtcta cagagttcag gaatatacag aagctacctg tggaaagtaa gagtgaagaa 2880

acaaatacag aaattgttga gtgcatccta aaaagaggtc agaaggcaac actactacaa 2940

caaaggagag aaggagagat gaaggaaata gaaagacctt ttgagacata taaggaaaat 3000

attgaattaa aagaaaacga tgaaaagatg aaagcaatga agagatcaag aacttggggg 3060

cagaaatgtg caccaatgtc tgacctgaca gacctcaaga gcttgcctga tacagaactc 3120

atgaaagaca cggcacgtgg ccagaatctc ctccaaaccc aagatcatgc caaggcacca 3180

aagagtgaga aaggcaaaat cactaaaatg ccctgccagt cattacaacc agaaccaata 3240

aacaccccaa cacacacaaa acaacagttg aaggcatccc tggggaaagt aggtgtgaaa 3300

gaagagctcc tagcagtcgg caagttcaca cggacgtcag gggagaccac gcacacgcac 3360

agagagccag caggagatgg caagagcatc agaacgttta aggagtctcc aaagcagatc 3420

ctggacccag cagcccgtgt aactggaatg aagaagtggc caagaacgcc taaggaagag 3480

gcccagtcac tagaagacct ggctggcttc aaagagctct tccagacacc aggtccctct 3540

gaggaatcaa tgactgatga gaaaactacc aaaatagcct gcaaatctcc accaccagaa 3600

tcagtggaca ctccaacaag cacaaagcaa tggcctaaga gaagtctcag gaaagcagat 3660

gtagaggaag aattcttagc actcaggaaa ctaacaccat cagcagggaa agccatgctt 3720

acgcccaaac cagcaggagg tgatgagaaa gacattaaag catttatggg aactccagtg 3780

cagaaactgg acctggcagg aactttacct ggcagcaaaa gacagctaca gactcctaag 3840

gaaaaggccc aggctctaga agacctggct ggctttaaag agctcttcca gactcctggt 3900

cacaccgagg aattagtggc tgctggtaaa accactaaaa taccctgcga ctctccacag 3960

tcagacccag tggacacccc aacaagcaca aagcaacgac ccaagagaag tatcaggaaa 4020

gcagatgtag agggagaact cttagcgtgc aggaatctaa tgccatcagc aggcaaagcc 4080

atgcacacgc ctaaaccatc agtaggtgaa gagaaagaca tcatcatatt tgtgggaact 4140

ccagtgcaga aactggacct gacagagaac ttaaccggca gcaagagacg gccacaaact 4200

cctaaggaag aggcccaggc tctggaagac ctgactggct ttaaagagct cttccagacc 4260

cctggtcata ctgaagaagc agtggctgct ggcaaaacta ctaaaatgcc ctgcgaatct 4320

tctccaccag aatcagcaga caccccaaca agcacaagaa ggcagcccaa gacacctttg 4380

gagaaaaggg acgtacagaa ggagctctca gccctgaaga agctcacaca gacatcaggg 4440

gaaaccacac acacagataa agtaccagga ggtgaggata aaagcatcaa cgcgtttagg 4500

gaaactgcaa aacagaaact ggacccagca gcaagtgtaa ctggtagcaa gaggcaccca 4560

aaaactaagg aaaaggccca acccctagaa gacctggctg gcttgaaaga gctcttccag 4620

acaccagtat gcactgacaa gcccacgact cacgagaaaa ctaccaaaat agcctgcaga 4680

tcacaaccag acccagtgga cacaccaaca agctccaagc cacagtccaa gagaagtctc 4740

aggaaagtgg acgtagaaga agaattcttc gcactcagga aacgaacacc atcagcaggc 4800

aaagccatgc acacacccaa accagcagta agtggtgaga aaaacatcta cgcatttatg 4860

ggaactccag tgcagaaact ggacctgaca gagaacttaa ctggcagcaa gagacggcta 4920

caaactccta aggaaaaggc ccaggctcta gaagacctgg ctggctttaa agagctcttc 4980

cagacacgag gtcacactga ggaatcaatg actaacgata aaactgccaa agtagcctgc 5040

aaatcttcac aaccagaccc agacaaaaac ccagcaagct ccaagcgacg gctcaagaca 5100

tccctgggga aagtgggcgt gaaagaagag ctcctagcag ttggcaagct cacacagaca 5160

tcaggagaga ctacacacac acacacagag ccaacaggag atggtaagag catgaaagca 5220

tttatggagt ctccaaagca gatcttagac tcagcagcaa gtctaactgg cagcaagagg 5280

cagctgagaa ctcctaaggg aaagtctgaa gtccctgaag acctggccgg cttcatcgag 5340

ctcttccaga caccaagtca cactaaggaa tcaatgacta acgaaaaaac taccaaagta 5400

tcctacagag cttcacagcc agacctagtg gacaccccaa caagctccaa gccacagccc 5460

aagagaagtc tcaggaaagc agacactgaa gaagaatttt tagcatttag gaaacaaacg 5520

ccatcagcag gcaaagccat gcacacaccc aaaccagcag taggtgaaga gaaagacatc 5580

aacacgtttt tgggaactcc agtgcagaaa ctggaccagc caggaaattt acctggcagc 5640

aatagacggc tacaaactcg taaggaaaag gcccaggctc tagaagaact gactggcttc 5700

agagagcttt tccagacacc atgcactgat aaccccacga ctgatgagaa aactaccaaa 5760

aaaatactct gcaaatctcc gcaatcagac ccagcggaca ccccaacaaa cacaaagcaa 5820

cggcccaaga gaagcctcaa gaaagcagac gtagaggaag aatttttagc attcaggaaa 5880

ctaacaccat cagcaggcaa agccatgcac acgcctaaag cagcagtagg tgaagagaaa 5940

gacatcaaca catttgtggg gactccagtg gagaaactgg acctgctagg aaatttacct 6000

ggcagcaaga gacggccaca aactcctaaa gaaaaggcca aggctctaga agatctggct 6060

ggcttcaaag agctcttcca gacaccaggt cacactgagg aatcaatgac cgatgacaaa 6120

atcacagaag tatcctgcaa atctccacaa ccagacccag tcaaaacccc aacaagctcc 6180

aagcaacgac tcaagatatc cttggggaaa gtaggtgtga aagaagaggt cctaccagtc 6240

ggcaagctca cacagacgtc agggaagacc acacagacac acagagagac agcaggagat 6300

ggaaagagca tcaaagcgtt taaggaatct gcaaagcaga tgctggaccc agcaaactat 6360

ggaactggga tggagaggtg gccaagaaca cctaaggaag aggcccaatc actagaagac 6420

ctggccggct tcaaagagct cttccagaca ccagaccaca ctgaggaatc aacaactgat 6480

gacaaaacta ccaaaatagc ctgcaaatct ccaccaccag aatcaatgga cactccaaca 6540

agcacaagga ggcggcccaa aacacctttg gggaaaaggg atatagtgga agagctctca 6600

gccctgaagc agctcacaca gaccacacac acagacaaag taccaggaga tgaggataaa 6660

ggcatcaacg tgttcaggga aactgcaaaa cagaaactgg acccagcagc aagtgtaact 6720

ggtagcaaga ggcagccaag aactcctaag ggaaaagccc aacccctaga agacttggct 6780

ggcttgaaag agctcttcca gacaccaata tgcactgaca agcccacgac tcatgagaaa 6840

actaccaaaa tagcctgcag atctccacaa ccagacccag tgggtacccc aacaatcttc 6900

aagccacagt ccaagagaag tctcaggaaa gcagacgtag aggaagaatc cttagcactc 6960

aggaaacgaa caccatcagt agggaaagct atggacacac ccaaaccagc aggaggtgat 7020

gagaaagaca tgaaagcatt tatgggaact ccagtgcaga aattggacct gccaggaaat 7080

ttacctggca gcaaaagatg gccacaaact cctaaggaaa aggcccaggc tctagaagac 7140

ctggctggct tcaaagagct cttccagaca ccaggcactg acaagcccac gactgatgag 7200

aaaactacca aaatagcctg caaatctcca caaccagacc cagtggacac cccagcaagc 7260

acaaagcaac ggcccaagag aaacctcagg aaagcagacg tagaggaaga atttttagca 7320

ctcaggaaac gaacaccatc agcaggcaaa gccatggaca caccaaaacc agcagtaagt 7380

gatgagaaaa atatcaacac atttgtggaa actccagtgc agaaactgga cctgctagga 7440

aatttacctg gcagcaagag acagccacag actcctaagg aaaaggctga ggctctagag 7500

gacctggttg gcttcaaaga actcttccag acaccaggtc acactgagga atcaatgact 7560

gatgacaaaa tcacagaagt atcctgtaaa tctccacagc cagagtcatt caaaacctca 7620

agaagctcca agcaaaggct caagataccc ctggtgaaag tggacatgaa agaagagccc 7680

ctagcagtca gcaagctcac acggacatca ggggagacta cgcaaacaca cacagagcca 7740

acaggagata gtaagagcat caaagcgttt aaggagtctc caaagcagat cctggaccca 7800

gcagcaagtg taactggtag caggaggcag ctgagaactc gtaaggaaaa ggcccgtgct 7860

ctagaagacc tggttgactt caaagagctc ttctcagcac caggtcacac tgaagagtca 7920

atgactattg acaaaaacac aaaaattccc tgcaaatctc ccccaccaga actaacagac 7980

actgccacga gcacaaagag atgccccaag acacgtccca ggaaagaagt aaaagaggag 8040

ctctcagcag ttgagaggct cacgcaaaca tcagggcaaa gcacacacac acacaaagaa 8100

ccagcaagcg gtgatgaggg catcaaagta ttgaagcaac gtgcaaagaa gaaaccaaac 8160

ccagtagaag aggaacccag caggagaagg ccaagagcac ctaaggaaaa ggcccaaccc 8220

ctggaagacc tggccggctt cacagagctc tctgaaacat caggtcacac tcaggaatca 8280

ctgactgctg gcaaagccac taaaataccc tgcgaatctc ccccactaga agtggtagac 8340

accacagcaa gcacaaagag gcatctcagg acacgtgtgc agaaggtaca agtaaaagaa 8400

gagccttcag cagtcaagtt cacacaaaca tcaggggaaa ccacggatgc agacaaagaa 8460

ccagcaggtg aagataaagg catcaaagca ttgaaggaat ctgcaaaaca gacaccggct 8520

ccagcagcaa gtgtaactgg cagcaggaga cggccaagag cacccaggga aagtgcccaa 8580

gccatagaag acctagctgg cttcaaagac ccagcagcag gtcacactga agaatcaatg 8640

actgatgaca aaaccactaa aataccctgc aaatcatcac cagaactaga agacaccgca 8700

acaagctcaa agagacggcc caggacacgt gcccagaaag tagaagtgaa ggaggagctg 8760

ttagcagttg gcaagctcac acaaacctca ggggagacca cgcacaccga caaagagccg 8820

gtaggtgagg gcaaaggcac gaaagcattt aagcaacctg caaagcggaa gctggacgca 8880

gaagatgtaa ttggcagcag gagacagcca agagcaccta aggaaaaggc ccaacccctg 8940

gaagatctgg ccagcttcca agagctctct caaacaccag gccacactga ggaactggca 9000

aatggtgctg ctgatagctt tacaagcgct ccaaagcaaa cacctgacag tggaaaacct 9060

ctaaaaatat ccagaagagt tcttcgggcc cctaaagtag aacccgtggg agacgtggta 9120

agcaccagag accctgtaaa atcacaaagc aaaagcaaca cttccctgcc cccactgccc 9180

ttcaagaggg gaggtggcaa agatggaagc gtcacgggaa ccaagaggct gcgctgcatg 9240

ccagcaccag aggaaattgt ggaggagctg ccagccagca agaagcagag ggttgctccc 9300

agggcaagag gcaaatcatc cgaacccgtg gtcatcatga agagaagttt gaggacttct 9360

gcaaaaagaa ttgaacctgc ggaagagctg aacagcaacg acatgaaaac caacaaagag 9420

gaacacaaat tacaagactc ggtccctgaa aataagggaa tatccctgcg ctccagacgc 9480

caaaataaga ctgaggcaga acagcaaata actgaggtct ttgtattagc agaaagaata 9540

gaaataaaca gaaatgaaaa gaagcccatg aagacctccc cagagatgga cattcagaat 9600

ccagatgatg gagcccggaa acccatacct agagacaaag tcactgagaa caaaaggtgc 9660

ttgaggtctg ctagacagaa tgagagctcc cagcctaagg tggcagagga gagcggaggg 9720

cagaagagtg cgaaggttct catgcagaat cagaaaggga aaggagaagc aggaaattca 9780

gactccatgt gcctgagatc aagaaagaca aaaagccagc ctgcagcaag cactttggag 9840

agcaaatctg tgcagagagt aacgcggagt gtcaagaggt gtgcagaaaa tccaaagaag 9900

gctgaggaca atgtgtgtgt caagaaaata agaaccagaa gtcataggga cagtgaagat 9960

atttgacaga aaaatcgaac tgggaaaaat ataataaagt tagttttgtg ataagttcta 10020

gtgcagtttt tgtcataaat tacaagtgaa ttctgtaagt aaggctgtca gtctgcttaa 10080

gggaagaaaa ctttggattt gctgggtctg aatcggcttc ataaactcca ctgggagcac 10140

tgctgggctc ctggactgag aatagttgaa caccgggggc tttgtgaagg agtctgggcc 10200

aaggtttgcc ctcagctttg cagaatgaag ccttgaggtc tgtcaccacc cacagccacc 10260

ctacagcagc cttaactgtg acacttgcca cactgtgtcg tcgtttgttt gcctatgtcc 10320

tccagggcac ggtggcagga acaactatcc tcgtctgtcc caacactgag caggcactcg 10380

gtaaacacga atgaatggat gagcgcacgg atgaatggag cttacaagat ctgtctttcc 10440

aatggccggg ggcatttggt ccccaaatta aggctattgg acatctgcac aggacagtcc 10500

tatttttgat gtcctttcct ttctgaaaat aaagttttgt gctttggaga atgactcgtg 10560

agcacatctt tagggaccaa gagtgacttt ctgtaaggag tgactcgtgg cttgccttgg 10620

tctcttggga atacttttct aactagggtt gctctcacct gagacattct ccacccgcgg 10680

aatctcaggg tcccaggctg tgggccatca cgacctcaaa ctggctccta atctccagct 10740

ttcctgtcat tgaaagcttc ggaagtttac tggctctgct cccgcctgtt ttctttctga 10800

ctctatctgg cagcccgatg ccacccagta caggaagtga caccagtact ctgtaaagca 10860

tcatcatcct tggagagact gagcactcag caccttcagc cacgatttca ggatcgcttc 10920

cttgtgagcc gctgcctccg aaatctcctt tgaagcccag acatctttct ccagcttcag 10980

acttgtagat ataactcgtt catcttcatt tactttccac tttgccccct gtcctctctg 11040

tgttccccaa atcagagaat agcccgccat cccccaggtc acctgtctgg attcctcccc 11100

attcacccac cttgccaggt gcaggtgagg atggtgcacc agacagggta gctgtccccc 11160

aaaatgtgcc ctgtgcgggc agtgccctgt ctccacgttt gtttccccag tgtctggcgg 11220

ggagccaggt gacatcataa atacttgctg aatgaatgca gaaatcagcg gtactgactt 11280

gtactatatt ggctgccatg atagggttct cacagcgtca tccatgatcg taagggagaa 11340

tgacattctg cttgagggag ggaatagaaa ggggcaggga ggggacatct gagggcttca 11400

cagggctgca aagggtacag ggattgcacc agggcagaac aggggagggt gttcaaggaa 11460

gagtggctct tagcagaggc actttggaag gtgtgaggca taaatgcttc cttctacgta 11520

ggccaacctc aaaactttca gtaggaatgt tgctatgatc aagttgttct aacactttag 11580

acttagtagt aattatgaac ctcacataga aaaatttcat ccagccatat gcctgtggag 11640

tggaatattc tgtttagtag aaaaatcctt tagagttcag ctctaaccag aaatcttgct 11700

gaagtatgtc agcacctttt ctcaccctgg taagtacagt atttcaagag cacgctaagg 11760

gtggttttca ttttacaggg ctgttgatga tgggttaaaa atgttcattt aagggctacc 11820

cccgtgttta atagatgaac accacttcta cacaaccctc cttggtactg ggggagggag 11880

agatctgaca aatactgccc attcccctag gctgactgga tttgagaaca aatacccacc 11940

catttccacc atggtatggt aacttctctg agcttcagtt tccaagtgaa tttccatgta 12000

ataggacatt cccattaaat acaagctgtt tttacttttt cgcctcccag ggcctgtggg 12060

atctggtccc ccagcctctc ttgggctttc ttacactaac tctgtaccta ccatctcctg 12120

cctcccttag gcaggcacct ccaaccacca cacactccct gctgttttcc ctgcctggaa 12180

ctttccctcc tgccccacca agatcatttc atccagtcct gagctcagct taagggaggc 12240

ttcttgcctg tgggttccct cacccccatg cctgtcctcc aggctggggc aggttcttag 12300

tttgcctgga attgttctgt acctctttgt agcacgtagt gttgtggaaa ctaagccact 12360

aattgagttt ctggctcccc tcctggggtt gtaagttttg ttcattcatg agggccgact 12420

gcatttcctg gttactctat cccagtgacc agccacagga gatgtccaat aaagtatgtg 12480

atgaaatggt cttaaaaaaa aaaaaaa 12507

<210> 137

<211> 3771

<212> DNA

<213>Homo sapiens

<400> 137

gcgccgggac gtggccagtt gcccgcctgc cccggagagc caggcgctaa ccagccgctc 60

tgcgccccgc gccctgcttg cccccattat ccagccttgc cccggcgccc tgacctgacg 120

ccctggcctg acgccctgct tcgtcgcctc ctttctctcc caggtgctgg accagggact 180

gagcgtcccc cggagagggt ccggtgtgac cccgacaaga agcagaaatg gggaagaaac 240

tggatctttc caagctcact gatgaagagg cccagcatgt cttggaagtt gttcaacgag 300

attttgacct ccgaaggaaa gaagaggaac ggctagaggc gttgaagggc aagattaaga 360

aggaaagctc caagagggag ctgctttccg acactgccca tctgaacgag acccactgcg 420

cccgctgcct gcagccctac cagctgcttg tgaatagcaa aaggcagtgc ctggaatgtg 480

gcctcttcac ctgcaaaagc tgtggccgcg tccacccgga ggagcagggc tggatctgtg 540

acccctgcca tctggccaga gtcgtgaaga tcggctcact ggagtggtac tatgagcatg 600

tgaaagcccg cttcaagagg ttcggaagtg ccaaggtcat ccggtccctc cacgggcggc 660

tgcagggtgg agctgggcct gaactgatat ctgaagagag aagtggagac agcgaccaga 720

cagatgagga tggagaacct ggctcagagg cccaggccca ggcccagccc tttggcagca 780

aaaaaaagcg cctcctctcc gtccacgact tcgacttcga gggagactca gatgactcca 840

ctcagcctca aggtcactcc ctgcacctgt cctcagtccc tgaggccagg gacagcccac 900

agtccctcac agatgagtcc tgctcagaga aggcagcccc tcacaaggct gagggcctgg 960

aggaggctga tactggggcc tctgggtgcc actcccatcc ggaagagcag ccgaccagca 1020

tctcaccttc cagacacggc gccctggctg agctctgccc gcctggaggc tcccacagga 1080

tggccctggg gactgctgct gcactcgggt cgaatgtcat caggaatgag cagctgcccc 1140

tgcagtactt ggccgatgtg gacacctctg atgaggaaag catccgggct cacgtgatgg 1200

cctcccacca ttccaagcgg agaggccggg cgtcttctga gagtcagatc tttgagctga 1260

ataagcatat ttcagctgtg gaatgcctgc tgacctacct ggagaacaca gttgtgcctc 1320

ccttggccaa gggtctaggt gctggagtgc gcacggaggc cgatgtagag gaggaggccc 1380

tgaggaggaa gctggaggag ctgaccagca acgtcagtga ccaggagacc tcgtccgagg 1440

aggaggaagc caaggacgaa aaggcagagc ccaacaggga caaatcagtt gggcctctcc 1500

cccaggcgga cccggaggtg ggcacggctg cccatcaaac caacagacag gaaaaaagcc 1560

cccaggaccc tggggacccc gtccagtaca acaggaccac agatgaggag ctgtcagagc 1620

tggaggacag agtggcagtg acggcctcag aagtccagca ggcagagagc gaggtttcag 1680

acattgaatc caggattgca gccctgaggg ccgcagggct cacggtgaag ccctcgggaa 1740

agccccggag gaagtcaaac ctcccgatat ttctccctcg agtggctggg aaacttggca 1800

agagaccaga ggacccaaat gcagaccctt caagtgaggc caaggcaatg gctgtgccct 1860

atcttctgag aagaaagttc agtaattccc tgaaaagtca aggtaaagat gatgattctt 1920

ttgatcggaa atcagtgtac cgaggctcgc tgacacagag aaaccccaac gcgaggaaag 1980

gaatggccag ccacaccttc gcgaaacctg tggtggccca ccagtcctaa cgggacagga 2040

cagagagaca gagcagccct gcactgtttt ccctccacca cagccatcct gtccctcatt 2100

ggctctgtgc tttccactat acacagtcac cgtcccaatg agaaacaaga aggagcaccc 2160

tccacatgga ctcccacctg caagtggaca gcgacattca gtcctgcact gctcacctgg 2220

gtttactgat gactcctggc tgccccacca tcctctctga tctgtgagaa acagctaagc 2280

tgctgtgact tccctttagg acaatgttgt gtaaatcttt gaaggacaca ccgaagacct 2340

ttatactgtg atcttttacc cctttcactc ttggctttct tatgttgctt tcatgaatgg 2400

aatggaaaaa agatgactca gttaaggcac cagccatatg tgtattcttg atggtctata 2460

tcggggtgtg agcagatgtt tgcgtatttc ttgtgggtgt gactggatat tagacatccg 2520

gacaagtgac tgaactaatg atctgctgaa taatgaagga ggaatagaca ccccagtccc 2580

caccctacgt gcacccgctc tgcaagttcc catgtgatct gtagaccagg ggaaattaca 2640

ctgcggtcaa gggcagagcc tgcacatgac agcaagtgag catttgatag atgctcagat 2700

gctagtgcag agagcctgct gggagacgaa gagacagcag gcagagctcc agatgggcaa 2760

ggaagaggct tggttctagc ctggctctgc ccctcactgc agtggatcca gtggggcaga 2820

ggacagaggg tcacaaccaa tgagggatgt ctgccaagga tgggggtgca gaggccacag 2880

gagtcagctt gccactcgcc cattggttac atagatgatc tctcagacag gctgggactc 2940

agagttattt cctagtatcg gtgtgcccca tccagtttta agtggagccc tccaagactc 3000

tccagagctg cctttgaaca tcctaacagt aatcacatct caccctccct gaggttcact 3060

ttagacagga cccaatggct gcactgcctt tgtcagaggg ggtgctgaga ggagtggctt 3120

cttttagaat caaacagtag agacaagagt caagccttgt gtcttcaagc attgaccaag 3180

ttaagtgttt ccttccctct ctcaataaga cacttccagg agctttccaa tctctcactt 3240

aaaactaagg tttgaatctc aaagtgttgc tgggaggctg atactcctgc aacttcagga 3300

gacctgtgag cacacattag cagctgtttc tctgactcct tgtggcatca gataaaaacg 3360

tgggagtttt tccatataat tcccagcctt acttataaat tctattcttt gaaaaaatta 3420

ttcaggctag gtaaggtggc tcatacctat aatcccagcc ctttgagagg ccaaggtggg 3480

agaattgctt gaggccagga gtttgagacc tcctgggcaa catagtgaga tcccatctct 3540

acaaaaaaca aaacaaaaaa attacccaag catgatggta tatgcctgta gtcgtaccta 3600

cttacttagg aggctgaggc aggaggatca cttgagccct ggaggttggg gctgcagtga 3660

gccatgatcg catcactata ctcgagcctg ggcaacagag tgagaccttg tctcttaaaa 3720

aaattaataa taaataaatg aaaataattc ttcagaaaaa aaaaaaaaaa a 3771

<210> 138

<211> 2240

<212> DNA

<213>Homo sapiens

<400> 138

aagcccagca gccccggggc ggatggctcc ggccgcctgg ctccgcagcg cggccgcgcg 60

cgccctcctg cccccgatgc tgctgctgct gctccagccg ccgccgctgc tggcccgggc 120

tctgccgccg gacgcccacc acctccatgc cgagaggagg gggccacagc cctggcatgc 180

agccctgccc agtagcccgg cacctgcccc tgccacgcag gaagcccccc ggcctgccag 240

cagcctcagg cctccccgct gtggcgtgcc cgacccatct gatgggctga gtgcccgcaa 300

ccgacagaag aggttcgtgc tttctggcgg gcgctgggag aagacggacc tcacctacag 360

gatccttcgg ttcccatggc agttggtgca ggagcaggtg cggcagacga tggcagaggc 420

cctaaaggta tggagcgatg tgacgccact cacctttact gaggtgcacg agggccgtgc 480

tgacatcatg atcgacttcg ccaggtactg gcatggggac gacctgccgt ttgatgggcc 540

tgggggcatc ctggcccatg ccttcttccc caagactcac cgagaagggg atgtccactt 600

cgactatgat gagacctgga ctatcgggga tgaccagggc acagacctgc tgcaggtggc 660

agcccatgaa tttggccacg tgctggggct gcagcacaca acagcagcca aggccctgat 720

gtccgccttc tacacctttc gctacccact gagtctcagc ccagatgact gcaggggcgt 780

tcaacaccta tatggccagc cctggcccac tgtcacctcc aggaccccag ccctgggccc 840

ccaggctggg atagacacca atgagattgc accgctggag ccagacgccc cgccagatgc 900

ctgtgaggcc tcctttgacg cggtctccac catccgaggc gagctctttt tcttcaaagc 960

gggctttgtg tggcgcctcc gtgggggcca gctgcagccc ggctacccag cattggcctc 1020

tcgccactgg cagggactgc ccagccctgt ggacgctgcc ttcgaggatg cccagggcca 1080

catttggttc ttccaaggtg ctcagtactg ggtgtacgac ggtgaaaagc cagtcctggg 1140

ccccgcaccc ctcaccgagc tgggcctggt gaggttcccg gtccatgctg ccttggtctg 1200

gggtcccgag aagaacaaga tctacttctt ccgaggcagg gactactggc gtttccaccc 1260

cagcacccgg cgtgtagaca gtcccgtgcc ccgcagggcc actgactgga gaggggtgcc 1320

ctctgagatc gacgctgcct tccaggatgc tgatggctat gcctacttcc tgcgcggccg 1380

cctctactgg aagtttgacc ctgtgaaggt gaaggctctg gaaggcttcc cccgtctcgt 1440

gggtcctgac ttctttggct gtgccgagcc tgccaacact ttcctctgac catggcttgg 1500

atgccctcag gggtgctgac ccctgccagg ccacgaatat caggctagag acccatggcc 1560

atctttgtgg ctgtgggcac caggcatggg actgagccca tgtctcctca gggggatggg 1620

gtggggtaca accaccatga caactgccgg gagggccacg caggtcgtgg tcacctgcca 1680

gcgactgtct cagactgggc agggaggctt tggcatgact taagaggaag ggcagtcttg 1740

ggcccgctat gcaggtcctg gcaaacctgg ctgccctgtc tccatccctg tccctcaggg 1800

tagcaccatg gcaggactgg gggaactgga gtgtccttgc tgtatccctg ttgtgaggtt 1860

ccttccaggg gctggcactg aagcaagggt gctggggccc catggccttc agccctggct 1920

gagcaactgg gctgtagggc agggccactt cctgaggtca ggtcttggta ggtgcctgca 1980

tctgtctgcc ttctggctga caatcctgga aatctgttct ccagaatcca ggccaaaaag 2040

ttcacagtca aatggggagg ggtattcttc atgcaggaga ccccaggccc tggaggctgc 2100

aacatacctc aatcctgtcc caggccggat cctcctgaag cccttttcgc agcactgcta 2160

tcctccaaag ccattgtaaa tgtgtgtaca gtgtgtataa accttcttct tctttttttt 2220

tttttaaact gaggattgtc 2240

<210> 139

<211> 3167

<212> DNA

<213>Homo sapiens

<400> 139

tagcagcaca caagggttcg tgtttgtgga accaggtagc ttccttcaga gctgacattt 60

gcccacagcc agcctggccc agccccatac caccagccct ggcgctctgg ggcgtgaggt 120

gccttttctg cccccctgct ctagggcagg tggaaatcac ccatggtggg tctacatctg 180

atagaagcat cttatagttc tgcttctgga ccagaccatc ctgggttttt ctctgttctg 240

ctgaagggtt ccctccacgt gtccatcacc tcggtgaact cttgggagac ctgggaagat 300

gctggcctca cctctcgcct ctcctttccc tcattgtgct gccaccatcc ttctcacaca 360

ggctctccag ggagagctgg gcaggatggg atcttcctgg gttcccacct tgctccgtgc 420

cccctctcac tgttcctgaa gtgtggccac ggactgcctt gttttctgga aagtcccaag 480

tctggaccat gactgagcag cattctcggc tatctgccac ctgtctgggg ctcctggccc 540

ctcttagact cccctctccc ttctgtttcc cccgagcccc tgacttggac ctgcagggtg 600

gggagaggga tgggacgaga acctgtgctg gggccaaagg tcgcactggg ggaaggtgga 660

gccagggcag cagagtgcct ggcgtcggcc cctatcctgt cactagttcc cccgttctgg 720

cccctggcag gtttgtaacc ccagatcaga agtactccat ggacaacact ccccacacgc 780

caaccccgtt caagaacgcc ctggagaagt acggacccct gaagcccctg gtacgtggtg 840

tggtcactgc cgtggatctc tgcacagtgg gatcccttcg gttcatccaa ccatgttcag 900

tccacaggac ccttccctct gaggtctcat ttgattcttt ctcctgagaa gatgcagaga 960

tcctgataat ataaatgggg aagctgaggc tgctctttgt cacttcctcc gactgctcct 1020

gagcacctga gtttgcaagc acgcgccggc tggtgctaga gacatggtgg tatcccgtga 1080

cactcagcct caggatgggg gagactgatg tgaaatacaa ataacttaaa cactttcagg 1140

caaagataag cactgggcct agttcagaga agtggcaaat tgctactctg gcctgtctct 1200

gaccaactcc cagttctcta cagagcacgg gaaagcccct cggggacgtc tttcctgcag 1260

tgtgcaggct gcccttctcc cctgctcttc ccagttgatg ggatggttgt gttttctcta 1320

tgaaaaaagg agttggcacc ttgggctttc tgaaacacac aggtgtttta gaaatcagtg 1380

gagggtgaga gaaaggcatg gttgtggagg cactggactg tgaacaaggt ctgcagcggg 1440

tccccctgct gtctctctct actgcatgga gcctcctatg aagcccaagg tggctggggg 1500

ctgaggctcc cttgggcctg ccatggaact gattctgagt caagcagact ttccacggac 1560

catgctacat gagccgaggt gaggcactag ttagtgctcc tttcctgttg cagtggagat 1620

ttggctcctc tgtactaaaa tatctgcatg ctctccaaac aggtgtgagg gcaaatcaca 1680

tgaccttggc agctgtaatt aaagtttgtg ggggcttttc ggatgactta tgaggagtgg 1740

ctgtgattcg cacctttcac tcttagtagc actcgccctc ccctgttctc tgttgcctga 1800

agctggagag gtccttggaa ccccgaggcc tgagaaaggg aaatgggttt gagagccccc 1860

attagtgtgg aacaaagggt tgagtgagcc tgggctttga gctgtcgggg tcctaattca 1920

gcagctgtgt gactgtgtgc caggctgttg atctctgagc ttctgtttct acctgcttaa 1980

aatgacggtt actgcacagg gctgtgtgag ggttacagtg cgtctctggg ctgctcccag 2040

ccatggcagg cccctgggaa tcaaggtcat cagctgcttg tccaaggcag cagttagtgg 2100

ttgtgaatgg tgcgtgtgag atctgcatcc tggcgtcagg cctccttcct gccttaccca 2160

ggacagccca gttgcagctg ggttggtccc acagtcccac acacacacag cccgagtgtg 2220

gtgcctcacg tgggctgccc cgtgcctacc cacagccaca gaccccgcac ctggaggagg 2280

acttgaagga ggtgctgcgt tctgaggctg gcatcgaact catcatcgag gacgacatca 2340

ggcccgagaa gcagaagagg aagcctgggc tgcggcggag ccccatcaag aaagtccgga 2400

agtctctggc tcttgacatt gtggatgagg atgtgaagct gatgatgtcc acactgccca 2460

agtctctatc cttgccgaca actgcccctt caaactcttc cagcctcacc ctgtcaggta 2520

tcaaagaaga caacagcttg ctcaaccagg gcttcttgca ggccaagccc gagaaggcag 2580

cagtggccca gaagccccga agccacttca cgacacctgc ccctatgtcc agtgcctgga 2640

agacggtggc ctgcgggggg accagggacc agcttttcat gcaggagaaa gcccggcagc 2700

tcctgggccg cctgaagccc agccacacat ctcggaccct catcttgtcc tgaggtgttg 2760

agggtgtcac gagcccattc acatgtttac aggggttgtg ggggcagagg gggtctgtga 2820

atctgagagt cattcaggtg acctcctgca gggagccttc tgccaccagc ccctccccag 2880

actctcaggt ggaggcaaca gggccatgtg ctgccctgtt gccgagccca gctgtgggcg 2940

gctcctggtg ctaacaacaa agttccactt ccaggtctgc ctggttcccc ccccaaggcc 3000

acagggagct ccgtcagctt ctcccaagcc cacgtcaggc ctggcctcat ctcagaccct 3060

gcttaggatg ggggatgtgg ccaggggtgc tcctgtgctc accctctctt ggtgcatttt 3120

tttggaagaa taaaattgcc tctctctttg aaaaaaaaaa aaaaaaa 3167

<210> 140

<211> 2379

<212> DNA

<213>Homo sapiens

<400> 140

gacccccgag ctgtgctgct cgcggccgcc accgccgggc cccggccgtc cctggctccc 60

ctcctgcctc gagaagggca gggcttctca gaggcttggc gggaaaaaga acggagggag 120

ggatcgcgct gagtataaaa gccggttttc ggggctttat ctaactcgct gtagtaattc 180

cagcgagagg cagagggagc gagcgggcgg ccggctaggg tggaagagcc gggcgagcag 240

agctgcgctg cgggcgtcct gggaagggag atccggagcg aatagggggc ttcgcctctg 300

gcccagccct cccgctgatc ccccagccag cggtccgcaa cccttgccgc atccacgaaa 360

ctttgcccat agcagcgggc gggcactttg cactggaact tacaacaccc gagcaaggac 420

gcgactctcc cgacgcgggg aggctattct gcccatttgg ggacacttcc ccgccgctgc 480

caggacccgc ttctctgaaa ggctctcctt gcagctgctt agacgctgga tttttttcgg 540

gtagtggaaa accagcagcc tcccgcgacg atgcccctca acgttagctt caccaacagg 600

aactatgacc tcgactacga ctcggtgcag ccgtatttct actgcgacga ggaggagaac 660

ttctaccagc agcagcagca gagcgagctg cagcccccgg cgcccagcga ggatatctgg 720

aagaaattcg agctgctgcc caccccgccc ctgtccccta gccgccgctc cgggctctgc 780

tcgccctcct acgttgcggt cacacccttc tcccttcggg gagacaacga cggcggtggc 840

gggagcttct ccacggccga ccagctggag atggtgaccg agctgctggg aggagacatg 900

gtgaaccaga gtttcatctg cgacccggac gacgagacct tcatcaaaaa catcatcatc 960

caggactgta tgtggagcgg cttctcggcc gccgccaagc tcgtctcaga gaagctggcc 1020

tcctaccagg ctgcgcgcaa agacagcggc agcccgaacc ccgcccgcgg ccacagcgtc 1080

tgctccacct ccagcttgta cctgcaggat ctgagcgccg ccgcctcaga gtgcatcgac 1140

ccctcggtgg tcttccccta ccctctcaac gacagcagct cgcccaagtc ctgcgcctcg 1200

caagactcca gcgccttctc tccgtcctcg gattctctgc tctcctcgac ggagtcctcc 1260

ccgcagggca gccccgagcc cctggtgctc catgaggaga caccgcccac caccagcagc 1320

gactctgagg aggaacaaga agatgaggaa gaaatcgatg ttgtttctgt ggaaaagagg 1380

caggctcctg gcaaaaggtc agagtctgga tcaccttctg ctggaggcca cagcaaacct 1440

cctcacagcc cactggtcct caagaggtgc cacgtctcca cacatcagca caactacgca 1500

gcgcctccct ccactcggaa ggactatcct gctgccaaga gggtcaagtt ggacagtgtc 1560

agagtcctga gacagatcag caacaaccga aaatgcacca gccccaggtc ctcggacacc 1620

gaggagaatg tcaagaggcg aacacacaac gtcttggagc gccagaggag gaacgagcta 1680

aaacggagct tttttgccct gcgtgaccag atcccggagt tggaaaacaa tgaaaaggcc 1740

cccaaggtag ttatccttaa aaaagccaca gcatacatcc tgtccgtcca agcagaggag 1800

caaaagctca tttctgaaga ggacttgttg cggaaacgac gagaacagtt gaaacacaaa 1860

cttgaacagc tacggaactc ttgtgcgtaa ggaaaagtaa ggaaaacgat tccttctaac 1920

agaaatgtcc tgagcaatca cctatgaact tgtttcaaat gcatgatcaa atgcaacctc 1980

acaaccttgg ctgagtcttg agactgaaag atttagccat aatgtaaact gcctcaaatt 2040

ggactttggg cataaaagaa cttttttatg cttaccatct tttttttttc tttaacagat 2100

ttgtatttaa gaattgtttt taaaaaattt taagatttac acaatgtttc tctgtaaata 2160

ttgccattaa atgtaaataa ctttaataaa acgtttatag cagttacaca gaatttcaat 2220

cctagtatat agtacctagt attataggta ctataaaccc taattttttt tatttaagta 2280

cattttgctt tttaaagttg atttttttct attgttttta gaaaaaataa aataactggc 2340

aaatatatca ttgagccaaa tcttaaaaaa aaaaaaaaa 2379

<210> 141

<211> 1799

<212> DNA

<213>Homo sapiens

<400> 141

gtgggaggat tgcattcagt ctagttcctg gttgccggct gaaataacct gctctccaaa 60

atgtccacaa aagtgactta agtcaggttc ccccaaacca gacaccaaga caagaatcca 120

tgtgtgtgtg actgaaggaa gtgctgggag agccccagct gcagcctgga tgtgaactgc 180

aactccaaag tgtgtccaga ctcaaggcaa gggcactagg ctttccagac ctcctactaa 240

gtcattgatc cagcactgcc ctgccaggac ataaatccct ggcacctctt gctctctgca 300

aaggagggca aagcagcttc aggagccctt gggagtcctc caaagagagt ctagggtaca 360

ggtccgaaag tagaagaaca cagaaggcag gccaggggca ctgtgagatg gtaaaagaga 420

tctgaaggga tccagaattc aagccaggaa gaagcagcaa tctgtcttct ggattaaaac 480

tgaagatcaa cctactttca acttactaag aaaggggatc atggacattg aagcatatct 540

tgaaagaatt ggctataaga agtctaggaa caaattggac ttggaaacat taactgatat 600

tcttcaacac cagatccgag ctgttccctt tgagaacctt aacatccatt gtggggatgc 660

catggactta ggcttagagg ccatttttga tcaagttgtg agaagaaatc ggggtggatg 720

gtgtctccag gtcaatcatc ttctgtactg ggctctgacc actattggtt ttgagaccac 780

gatgttggga gggtatgttt acagcactcc agccaaaaaa tacagcactg gcatgattca 840

ccttctcctg caggtgacca ttgatggcag gaactacatt gtcgatgctg ggtttggacg 900

ctcataccag atgtggcagc ctctggagtt aatttctggg aaggatcagc ctcaggtgcc 960

ttgtgtcttc cgtttgacgg aagagaatgg attctggtat ctagaccaaa tcagaaggga 1020

acagtacatt ccaaatgaag aatttcttca ttctgatctc ctagaagaca gcaaataccg 1080

aaaaatctac tcctttactc ttaagcctcg aacaattgaa gattttgagt ctatgaatac 1140

atacctgcag acatctccat catctgtgtt tactagtaaa tcattttgtt ccttgcagac 1200

cccagatggg gttcactgtt tggtgggctt caccctcacc cataggagat tcaattataa 1260

ggacaataca gatctaatag agttcaagac tctgagtgag gaagaaatag aaaaagtgct 1320

gaaaaatata tttaatattt ccttgcagag aaagcttgtg cccaaacatg gtgatagatt 1380

ttttactatt tagaataagg agtaaaacaa tcttgtctat ttgtcatcca gctcaccagt 1440

tatcaactga cgacctatca tgtatcttct gtacccttac cttattttga agaaaatcct 1500

agacatcaaa tcatttcacc tataaaaatg tcatcatata taattaaaca gctttttaaa 1560

gaaacataac cacaaacctt ttcaaataat aataataata ataataataa atgtctttta 1620

aagatggcct gtggttatct tggaaattgg tgatttatgc tagaaagctt ttaatgttgg 1680

tttattgttg aattcctaga aaagttttat gggtagatga gtaaataaaa tattgtaaaa 1740

aaacttattg tctataaagt atattaaaac attgttggct aatataaaaa aaaaaaaaa 1799

<210> 142

<211> 1644

<212> DNA

<213>Homo sapiens

<400> 142

gcgcgcgggt ttcgttgacc cgcggcgttc acgggaattg ttcgctttag tgccggcgcc 60

atggggtcgg agctgatcgg gcgcctagcc ccgcgcctgg gcctcgccga gcccgacatg 120

ctgaggaaag cagaggagta cttgcgcctg tcccgggtga agtgtgtcgg cctctccgca 180

cgcaccacgg agaccagcag tgcagtcatg tgcctggacc ttgcagcttc ctggatgaag 240

tgccccttgg acagggctta tttaattaaa ctttctggtt tgaacaagga gacatatcag 300

agctgtctta aatcttttga gtgtttactg ggcctgaatt caaatattgg aataagagac 360

ctagctgtac agtttagctg tatagaagca gtgaacatgg cttcaaagat actaaaaagc 420

tatgagtcca gtcttcccca gacacagcaa gtggatcttg acttatccag gccacttttc 480

acttctgctg cactgctttc agcatgcaag attctaaagc tgaaagtgga taaaaacaaa 540

atggtagcca catccggtgt aaaaaaagct atatttgatc gactgtgtaa acaactagag 600

aagattggac agcaggtcga cagagaacct ggagatgtag ctactccacc acggaagaga 660

aagaagatag tggttgaagc cccagcaaag gaaatggaga aggtagagga gatgccacat 720

aaaccacaga aagatgaaga tctgacacag gattatgaag aatggaaaag aaaaattttg 780

gaaaatgctg ccagtgctca aaaggctaca gcagagtgat ttcagcttcc aaactggtat 840

acattccaaa ctgatagtac attgccatct ccaggaagac ttgacggctt tgggattttg 900

tttaaacttt tataataagg atcctaagac tgttgccttt aaatagcaaa gcagcctacc 960

tggaggctaa gtctgggcag tgggctggcc cctggtgtga gcattagacc agccacagtg 1020

cctgattggt atagccttat gtgctttcct acaaaatgga attggaggcc gggcgcagtg 1080

gctcacgcct gtaatcccag cactttggga ggccaaggtg ggtggatcac ctgaggtcag 1140

gagctcgaga ccagcctggc caacatggtg aaaccccatc tctactaaaa atacaaaaat 1200

tagccaggtg tgatggtgca tgcctgtaat cccagctcct cagtaggctg agacaggagc 1260

atcacttgaa cgtgggaggc agaggttgca gtgagccgag attgcaccac cgcactccag 1320

cctgggtgac agagcgagac ttatctcata aataaataga tagatactcc agcctgggtg 1380

acagagcgag acttatagat agatagatag atagatggat agatagatag atagatagat 1440

agatagataa acggaattgg agccattttg ctttaagtga atggcagtcc cttgtcttat 1500

tcagaatata aaattcagtc tgaatggcat cttacagatt ttacttcaat ttttgtgtac 1560

ggtatttttt atttgactaa atcaatatat tgtacagcct aagttaataa atgttattta 1620

tatatgcaaa aaaaaaaaaa aaaa 1644

<210> 143

<211> 13037

<212> DNA

<213>Homo sapiens

<400> 143

agtccacagc tgtcactaat cggggtaagc cttgttgtat ttgtgcgtgt gggtggcatt 60

ctcaatgaga actagcttca cttgtcattt gagtgaaatc tacaacccga ggcggctagt 120

gctcccgcac tactgggatc tgagatcttc ggagatgact gtcgcccgca gtacggagcc 180

agcagaagtc cgacccttcc tgggaatggg ctgtaccgag aggtccgact agccccaggg 240

ttttagtgag ggggcagtgg aactcagcga gggactgaga gcttcacagc atgcacgagt 300

ttgatgccag agaaaaagtc gggagataaa ggagccgcgt gtcactaaat tgccgtcgca 360

gccgcagcca ctcaagtgcc ggacttgtga gtactctgcg tctccagtcc tcggacagaa 420

gttggagaac tctcttggag aactccccga gttaggagac gagatctcct aacaattact 480

actttttctt gcgctcccca cttgccgctc gctgggacaa acgacagcca cagttcccct 540

gacgacagga tggaggccaa gggcaggagc tgaccagcgc cgccctcccc cgcccccgac 600

ccaggaggtg gagatccctc cggtccagcc acattcaaca cccactttct cctccctctg 660

cccctatatt cccgaaaccc cctcctcctt cccttttccc tcctcctgga gacgggggag 720

gagaaaaggg gagtccagtc gtcatgactg agctgaaggc aaagggtccc cgggctcccc 780

acgtggcggg cggcccgccc tcccccgagg tcggatcccc actgctgtgt cgcccagccg 840

caggtccgtt cccggggagc cagacctcgg acaccttgcc tgaagtttcg gccataccta 900

tctccctgga cgggctactc ttccctcggc cctgccaggg acaggacccc tccgacgaaa 960

agacgcagga ccagcagtcg ctgtcggacg tggagggcgc atattccaga gctgaagcta 1020

caaggggtgc tggaggcagc agttctagtc ccccagaaaa ggacagcgga ctgctggaca 1080

gtgtcttgga cactctgttg gcgccctcag gtcccgggca gagccaaccc agccctcccg 1140

cctgcgaggt caccagctct tggtgcctgt ttggccccga acttcccgaa gatccaccgg 1200

ctgcccccgc cacccagcgg gtgttgtccc cgctcatgag ccggtccggg tgcaaggttg 1260

gagacagctc cgggacggca gctgcccata aagtgctgcc ccggggcctg tcaccagccc 1320

ggcagctgct gctcccggcc tctgagagcc ctcactggtc cggggcccca gtgaagccgt 1380

ctccgcaggc cgctgcggtg gaggttgagg aggaggatgg ctctgagtcc gaggagtctg 1440

cgggtccgct tctgaagggc aaacctcggg ctctgggtgg cgcggcggct ggaggaggag 1500

ccgcggctgt cccgccgggg gcggcagcag gaggcgtcgc cctggtcccc aaggaagatt 1560

cccgcttctc agcgcccagg gtcgccctgg tggagcagga cgcgccgatg gcgcccgggc 1620

gctccccgct ggccaccacg gtgatggatt tcatccacgt gcctatcctg cctctcaatc 1680

acgccttatt ggcagcccgc actcggcagc tgctggaaga cgaaagttac gacggcgggg 1740

ccggggctgc cagcgccttt gccccgccgc ggagttcacc ctgtgcctcg tccaccccgg 1800

tcgctgtagg cgacttcccc gactgcgcgt acccgcccga cgccgagccc aaggacgacg 1860

cgtaccctct ctatagcgac ttccagccgc ccgctctaaa gataaaggag gaggaggaag 1920

gcgcggaggc ctccgcgcgc tccccgcgtt cctaccttgt ggccggtgcc aaccccgcag 1980

ccttcccgga tttcccgttg gggccaccgc ccccgctgcc gccgcgagcg accccatcca 2040

gacccgggga agcggcggtg acggccgcac ccgccagtgc ctcagtctcg tctgcgtcct 2100

cctcggggtc gaccctggag tgcatcctgt acaaagcgga gggcgcgccg ccccagcagg 2160

gcccgttcgc gccgccgccc tgcaaggcgc cgggcgcgag cggctgcctg ctcccgcggg 2220

acggcctgcc ctccacctcc gcctctgccg ccgccgccgg ggcggccccc gcgctctacc 2280

ctgcactcgg cctcaacggg ctcccgcagc tcggctacca ggccgccgtg ctcaaggagg 2340

gcctgccgca ggtctacccg ccctatctca actacctgag gccggattca gaagccagcc 2400

agagcccaca atacagcttc gagtcattac ctcagaagat ttgtttaatc tgtggggatg 2460

aagcatcagg ctgtcattat ggtgtcctta cctgtgggag ctgtaaggtc ttctttaaga 2520

gggcaatgga agggcagcac aactacttat gtgctggaag aaatgactgc atcgttgata 2580

aaatccgcag aaaaaactgc ccagcatgtc gccttagaaa gtgctgtcag gctggcatgg 2640

tccttggagg tcgaaaattt aaaaagttca ataaagtcag agttgtgaga gcactggatg 2700

ctgttgctct cccacagcca gtgggcgttc caaatgaaag ccaagcccta agccagagat 2760

tcactttttc accaggtcaa gacatacagt tgattccacc actgatcaac ctgttaatga 2820

gcattgaacc agatgtgatc tatgcaggac atgacaacac aaaacctgac acctccagtt 2880

ctttgctgac aagtcttaat caactaggcg agaggcaact tctttcagta gtcaagtggt 2940

ctaaatcatt gccaggtttt cgaaacttac atattgatga ccagataact ctcattcagt 3000

attcttggat gagcttaatg gtgtttggtc taggatggag atcctacaaa cacgtcagtg 3060

ggcagatgct gtattttgca cctgatctaa tactaaatga acagcggatg aaagaatcat 3120

cattctattc attatgcctt accatgtggc agatcccaca ggagtttgtc aagcttcaag 3180

ttagccaaga agagttcctc tgtatgaaag tattgttact tcttaataca attcctttgg 3240

aagggctacg aagtcaaacc cagtttgagg agatgaggtc aagctacatt agagagctca 3300

tcaaggcaat tggtttgagg caaaaaggag ttgtgtcgag ctcacagcgt ttctatcaac 3360

ttacaaaact tcttgataac ttgcatgatc ttgtcaaaca acttcatctg tactgcttga 3420

atacatttat ccagtcccgg gcactgagtg ttgaatttcc agaaatgatg tctgaagtta 3480

ttgctgcaca attacccaag atattggcag ggatggtgaa accccttctc tttcataaaa 3540

agtgaatgtc atctttttct tttaaagaat taaattttgt ggtatgtctt tttgttttgg 3600

tcaggattat gaggtcttga gtttttataa tgttcttctg aaagccttac atttataaca 3660

tcatagtgtg taaatttaaa agaaaaattg tgaggttcta attattttct tttataaagt 3720

ataattagaa tgtttaactg ttttgtttac ccatattttc ttgaagaatt tacaagattg 3780

aaaaagtact aaaattgtta aagtaaacta tcttatccat attatttcat accatgtagg 3840

tgaggatttt taacttttgc atctaacaaa tcatcgactt aagagaaaaa atcttacatg 3900

taataacaca aagctattat atgttatttc taggtaactc cctttgtgtc aattatattt 3960

ccaaaaatga acctttaaaa tggtatgcaa aattttgtct atatatattt gtgtgaggag 4020

gaaattcata actttcctca gattttcaaa agtattttta atgcaaaaaa tgtagaaaga 4080

gtttaaaacc actaaaatag attgatgttc ttcaaactag gcaaaacaac tcatatgtta 4140

agaccatttt ccagattgga aacacaaatc tcttaggaag ttaataagta gattcatatc 4200

attatgcaaa tagtattgtg ggttttgtag gtttttaaaa taaccttttt tggggagaga 4260

attgtcctct aatgaggtat tgcgagtgga cataagaaat cagaagatta tggcctaact 4320

gtactcctta ccaactgtgg catgctgaaa gttagtcact cttactgatt ctcaattctc 4380

tcacctttga aagtagtaaa atatctttcc tgccaattgc tcctttgggt cagagcttat 4440

taacatcttt tcaaatcaaa ggaaagaaga aagggagagg aggaggaggg aggtatcaat 4500

tcacatacct ttctcctctt tatcctccac tatcatgaat tcatattatg tttcagccat 4560

gcaaatcttt ttaccatgaa atttcttcca gaattttccc cctttgacac aaattccatg 4620

catgtttcaa ccttcgagac tcagccaaat gtcatttctg taaaatcttc cctgagtctt 4680

ccaagcagta atttgccttc tcctagagtt tacctgccat tttgtgcaca tttgagttac 4740

agtagcatgt tattttacaa ttgtgactct cctgggagtc tgggagccat ataaagtggt 4800

caatagtgtt tgctgactga gagttgaatg acattttctc tctgtcttgg tattactgta 4860

gatttcgatc attctttggt tacatttctg catatttctg tacccatgac tttatcactt 4920

tcttctccca tgctttatct ccatcaatta tcttcattac ttttaaattt tccacctttg 4980

cttcctactt tgtgagatct ctccctttac tgactataac atagaagaat agaagtgtat 5040

tttatgtgtc ttaaggacaa tactttagat tccttgttct aagtttttaa actgaatgaa 5100

tggaatatta tttctctccc taagcaaaat tccacaaaac aattatttct tatgtttatg 5160

tagccttaaa ttgttttgta ctgtaaacct cagcataaaa actttcttca tttctaattt 5220

cattcaacaa atattgattg aatacctggt attagcacaa gaaaaatgtg ctaataagcc 5280

ttatgagaat ttggagctga agaaagacat ataactcagg aaagttacag tccagtagta 5340

ggtataaatt acagtgcctg ataaataggc attttaatat ttgtacactc aacgtatact 5400

aggtaggtgc aaaacattta catataattt tactgatacc catgcagcac aaaggtacta 5460

actttaaata ttaaataaca cctttatgtg tcagtaattc atttgcatta aatcttattg 5520

aaaaggcttt caatatattt tccccacaaa tgtcatccca agaaaaaagt atttttaaca 5580

tctcccaaat ataatagtta caggaaatct acctctgtga gagtgacacc tctcagaatg 5640

aactgtgtga cacaagaaaa tgaatgtagg tctatccaaa aaaaacccca agaaacaaaa 5700

acaatattat tagcccttta tgcttaagtg atggactcag ggaacagttg atgttgtgat 5760

cattttatta tctgattctt gttactttga attaaaccaa tattttgatg atataaatca 5820

tttccaccag catatattta atttccataa taactttaaa attttctaat ttcactcaac 5880

tatgagggaa tagaatgtgg tggccacagg tttggctttt gttaaaatgt ttgatatctt 5940

cgatgttgat ctctgtctgc aatgtagatg tctaaacact aggatttaat atttaaggct 6000

aagctttaaa aataaagtac ctttttaaaa agaatatggc ttcaccaaat ggaaaatacc 6060

taatttctaa atctttttct ctacaaagtc ctatctacta atgtctccat tactatttag 6120

tcatcataac cattatcttc attttacatg tcgtgttctt tctggtagct ctaaaatgac 6180

actaaatcat aagaagacag gttacatatc aggaaatact tgaaggttac tgaaatagat 6240

tcttgagtta atgaaaatat tttctgtaaa aaggtttgaa aagccatttg agtctaaagc 6300

attatacctc cattatcagt agttatgtga caattgtgtg tgtgtttaat gtttaaagat 6360

gtggcacttt ttaataaggc aatgctatgc tattttttcc catttaacat taagataatt 6420

tattgctata cagatgatat ggaaatatga tgaacaatat tttttttgcc aaaactatgc 6480

cttgtaagta gccatggaat gtcaacctgt aacttaaatt atccacagat agtcatgtgt 6540

ttgatgatgg gcactgtgga gataactgac ataggactgt gccccccttc tctgccactt 6600

actagctgga tgagattaag caagtcattt aactgctctg attaaacctg cctttcccaa 6660

gtgctttgta atgaatagaa atggaaacca aaaaaaacgt atacaggcct tcagaaatag 6720

taattgctac tattttgttt tcattaagcc atagttctgg ctataatttt atcaaactca 6780

ccagctatat tctacagtga aagcaggatt ctagaaagtc tcactgtttt atttatgtca 6840

ccatgtgcta tgatatattt ggttgaattc atttgaaatt agggctggaa gtattcaagt 6900

aatttcttct gctgaaaaaa tacagtgttt tgagtttagg gcctgtttta tcaaagttct 6960

aaagagccta tcactcttcc attgtagaca ttttaaaata atgacactga ttttaacatt 7020

tttaagtgtc tttttagaac agagagcctg actagaacac agcccctcca aaaacccatg 7080

ctcaaattat ttttactatg gcagcaattc cacaaaaggg aacaatgggt ttagaaatta 7140

caatgaagtc atcaacccaa aaaacatccc tatccctaag aaggttatga tataaaatgc 7200

ccacaagaaa tctatgtctg ctttaatctg tcttttattg ctttggaagg atggctatta 7260

catttttagt ttttgctgtg aatacctgag cagtttctct catccatact tatccttcac 7320

acatcagaag tcaggataga atatgaatca ttttaaaaac ttttacaact ccagagccat 7380

gtgcataaga agcattcaaa acttgccaaa acatacattt tttttcaaat ttaaagatac 7440

tctatttttg tattcaatag ctcaacaact gtggtcccca ctgataaagt gaagtggaca 7500

aggagacaag taatggcata agtttgtttt tcccaaagta tgcctgttca atagccattg 7560

gatgtgggaa atttctacat ctcttaaaat tttacagaaa atacatagcc agatagtcta 7620

gcaaaagttc accaagtcct aaattgctta tccttacttc actaagtcat gaaatcattt 7680

taatgaaaag aacatcacct aggttttgtg gtttcttttt ttcttattca tggctgagtg 7740

aaaacaacaa tctctgtttc tccctagcat ctgtggacta tttaatgtac cattattcca 7800

cactctatgg tccttactaa atacaaaatt gaacaaaaag cagtaaaaca actgactctt 7860

cacccatatt ataaaatata atccaagcca gattagtcaa catccataag atgaatccaa 7920

gctgaactgg gcctagatta ttgagttcag gttggatcac atccctattt attaataaac 7980

ttaggaaaga aggccttaca gaccatcagt tagctggagc taatagaacc tacacttcta 8040

aagttcggcc tagaatcaat gtggccttaa aagctgaaaa gaagcaggaa agaacagttt 8100

tcttcaataa tttgtccacc ctgtcactgg agaaaattta agaatttggg ggtgttggta 8160

gtaagttaaa cacagcagct gttcatggca gaaattattc aatacatacc ttctctgaat 8220

atcctataac caaagcaaag aaaaacacca aggggtttgt tctcctcctt ggagttgacc 8280

tcattccaag gcagagctca ggtcacaggc acaggggctg cgcccaagct tgtccgcagc 8340

cttatgcagc tgtggagtct ggaagactgt tgcaggactg ctggcctagt cccagaatgt 8400

cagcctcatt ttcgatttac tggctcttgt tgctgtatgt catgctgacc ttattgttaa 8460

acacaggttt gtttgctttt tttccactca tggagacatg ggagaggcat tatttttaag 8520

ctggttgaaa gctttaaccg ataaagcatt tttagagaaa tgtgaatcag gcagctaaga 8580

aagcatactc tgtccattac ggtaaagaaa atgcacagat tattaactct gcagtgtggc 8640

attagtgtcc tggtcaatat tcggatagat atgaataaaa tatttaaatg gtattgtaaa 8700

tagttttcag gacatatgct atagcttatt tttattatct tttgaaattg ctcttaatac 8760

atcaaatcct gatgtattca atttatcaga tataaattat tctaaatgaa gcccagttaa 8820

atgtttttgt cttgtcagtt atatgttaag tttctgatct ctttgtctat gacgtttact 8880

aatctgcatt tttactgtta tgaattattt tagacagcag tggtttcaag ctttttgcca 8940

ctaaaaatac cttttatttt ctcctccccc agaaaagtct ataccttgaa gtatctatcc 9000

accaaactgt acttctatta agaaatagtt attgtgtttt cttaatgttt tgttattcaa 9060

agacatatca atgaaagctg ctgagcagca tgaataacaa ttatatccac acagatttga 9120

tatattttgt gcagccttaa cttgatagta taaaatgtca ttgcttttta aataatagtt 9180

agtcaatgga cttctatcat agctttccta aactaggtta agatccagag ctttggggtc 9240

ataatatatt acatacaatt aagttatctt tttctaaggg ctttaaaatt catgagaata 9300

accaaaaaag gtatgtggag agttaataca aacataccat attcttgttg aaacagagat 9360

gtggctctgc ttgttctcca taaggtagaa atactttcca gaatttgcct aaactagtaa 9420

gccctgaatt tgctatgatt agggatagga agagattttc acatggcaga ctttagaatt 9480

cttcacttta gccagtaaag tatctccttt tgatcttagt attctgtgta ttttaacttt 9540

tctgagttgt gcatgtttat aagaaaaatc agcacaaagg gtttaagtta aagccttttt 9600

actgaaattt gaaagaaaca gaagaaaata tcaaagttct ttgtattttg agaggattaa 9660

atatgattta caaaagttac atggagggct ctctaaaaca ttaaattaat tattttttgt 9720

tgaaaagtct tactttaggc atcattttat tcctcagcaa ctagctgtga agcctttact 9780

gtgctgtatg ccagtcactc tgctagattg tggagattac cagtgttccc gtcttctccg 9840

agcttagagt tggatgggga ataaagacag gtaaacagat agctacaata ttgtactgtg 9900

aatgcttatg ctggaggaag tacagggaac tattggagca cctaagagga gcacctacct 9960

tgaatttagg ggttagcaga ggcatcctga aaaaagtcaa agctaagcca caatctataa 10020

gcagtttagg aattagcaga acgtgcgtgg tgaggagatg ccaaaggcaa gaagagaaga 10080

gtattccaaa caggagggat tccaaagaga gaagagtatc ccaaacaaca tttgcacaaa 10140

cctgatgggg agagagaatg tggggtgggg atggatgatg agactgaaga agaaagccag 10200

gtctagataa tcagtggcct tgtacaccat gttaaagagt gtagacttga ttctgttgta 10260

aacaggaaag cagcacaatt catatgaata ttttagaaga ctcccactgg aatatggaga 10320

ataaagttgg agatgactaa tcctggaagc agggagaaca tttttgagga agttgcacta 10380

ttttggtgaa aatgatgatc ataaacatga agaattgtag gtgatcatga cctcctctct 10440

aattttccag aagggttttg gaagatataa cataggaaca ttgacaggac tgacgaaagg 10500

agatgaaata caccatataa attgtcaaac acaaggccag atgtctaatt attttgctta 10560

tgtgttgaaa ttacaaattt ttcatcagga aaccaaaaac tacaaaactt agttttccca 10620

agtcccagaa ttctatctgt ccaaacaatc tgtaccactc cacctatatc cctacctttg 10680

catgtctgtc caacctcaaa gtccaggtct atacacacgg gtaagactag agcagttcaa 10740

gtttcagaaa atgagaaaga ggaactgagt tgtgctgaac ccatacaaaa taaacacatt 10800

ctttgtatag attcttggaa cctcgagagg aattcaccta actcataggt atttgatggt 10860

atgaatccat ggctgggctc ggcttttaaa aagccttatc tgggattcct tctatggaac 10920

caagttccat caaagcccat ttaaaagcct acattaaaaa caaaattctt gctgcattgt 10980

atacaaataa tgatgtcatg atcaaataat cagatgccat tatcaagtgg aattacaaaa 11040

tggtataccc actccaaaaa aaaaaaaaaa gctaaattct cagtagaaca ttgtgacttc 11100

atgagccctc cacagccttg gagctgagga gggagcactg gtgagcagta ggttgaagag 11160

aaaacttggc gcttaataat ctatccatgt tttttcatct aaaagagcct tctttttgga 11220

ttaccttatt caatttccat caaggaaatt gttagttcca ctaaccagac agcagctggg 11280

aaggcagaag cttactgtat gtacatggta gctgtgggaa ggaggtttct ttctccaggt 11340

cctcactggc catacaccag tcccttgtta gttatgcctg gtcatagacc cccgttgcta 11400

tcatctcata tttaagtctt tggcttgtga atttatctat tctttcagct tcagcactgc 11460

agagtgctgg gactttgcta acttccattt cttgctggct tagcacattc ctcataggcc 11520

cagctctttt ctcatctggc cctgctgtgg agtcaccttg ccccttcagg agagccatgg 11580

cttaccactg cctgctaagc ctccactcag ctgccaccac actaaatcca agcttctcta 11640

agatgttgca gactttacag gcaagcataa aaggcttgat cttcctggac ttccctttac 11700

ttgtctgaat ctcacctcct tcaactttca gtctcagaat gtaggcattt gtcctctttg 11760

ccctacatct tccttcttct gaatcatgaa agcctctcac ttcctcttgc tatgtgctgg 11820

aggcttctgt caggttttag aatgagttct catctagtcc tagtagcttt tgatgcttaa 11880

gtccaccttt taaggatacc tttgagattt agaccatgtt tttcgcttga gaaagcccta 11940

atctccagac ttgcctttct gtggatttca aagaccaact gaggaagtca aaagctgaat 12000

gttgactttc tttgaacatt tccgctataa caattccaat tctcctcaga gcaatatgcc 12060

tgcctccaac tgaccaggag aaaggtccag tgccaaagag aaaaacacaa agattaatta 12120

tttcagttga gcacatactt tcaaagtggt ttgggtattc atatgaggtt ttctgtcaag 12180

agggtgagac tcttcatcta tccatgtgtg cctgacagtt ctcctggcac tggctggtaa 12240

cagatgcaaa actgtaaaaa ttaagtgatc atgtatttta acgatatcat cacatactta 12300

ttttctatgt aatgttttaa atttccccta acatactttg actgttttgc acatggtaga 12360

tattcacatt tttttgtgtt gaagttgatg caatcttcaa agttatctac cccgttgctt 12420

attagtaaaa ctagtgttaa tacttggcaa gagatgcagg gaatctttct catgactcac 12480

gccctattta gttattaatg ctactaccct attttgagta agtagtaggt ccctaagtac 12540

attgtccaga gttatacttt taaagatatt tagccccata tacttcttga atctaaagtc 12600

atacaccttg ctcctcattt ctgagtggga aagacatttg agagtatgtt gacaattgtt 12660

ctgaaggttt ttgccaagaa ggtgaaactg tcctttcatc tgtgtatgcc tggggctggg 12720

tccctggcag tgatggggtg acaatgcaaa gctgtaaaaa ctaggtgcta gtgggcacct 12780

aatatcatca tcatatactt attttcaagc taatatgcaa aatcccatct ctgtttttaa 12840

actaagtgta gatttcagag aaaatatttt gtggttcaca taagaaaaca gtctactcag 12900

cttgacaagt gttttatgtt aaattggctg gtggtttgaa atgaatcatc ttcacataat 12960

gttttcttta aaaatattgt gaatttaact ctaattcttg ttattctgtg tgataataaa 13020

gaataaacta atttcta 13037

<210> 144

<211> 3180

<212> DNA

<213>Homo sapiens

<400> 144

attctatgct gcagcctaag catcattcct cttctcttct tagtggagat aaaattaccc 60

actgctctcc ttacatttac tttgtccata tttgctccta tgctctaggc tcgtgcacaa 120

caaacacagt gtgggccctt accctagaag ccaacttctc atgacctttc tctatctcca 180

gaatccatgc agtgggaatg aaggtaaaag aaggttttca tgggatccag ctgagagctc 240

tacggggaaa atggatctga ggagccatgt gctccatctc ttttatttta caggtagaga 300

ctaggggtat agagtgaggt gaattaccgc agtgacccac acattgttgg cagacctagg 360

attagaactc tgtcttcctg gttcccagct tggtgctttt gaaagcatac ttgctgcttt 420

cttaccggcc tggtgtctgc cactttggga cagagtgtgg acttgctcac ctgccccatt 480

tcttagggat tctcattctg tgtttgagca agaatattct tattctggaa agaaccacat 540

accacaggat tctgggtgag cataaggaag attgtcttgg ggatctgact tagctcacgt 600

atagtggcta tgatgaattc agtgtcttat tttttgcata tgtatatttt tagtctaata 660

ttgcctgggt gtctgagcaa gtctagatga atttaattgc tctcattttt cccctgcccc 720

tcttcctttg gtctctcttt taggaaatgt ttttctttca acattcgttt cattcattat 780

ttactcattc ggccaaccaa catttattga gtgccttccc tgtatcaggg acaggggctt 840

acaaagtaga atttgatccc acctctgccc tcagtagctc agtgtctaat ggaggtagtg 900

atgttcatta agcgtcgcca gatactgtgc taggtgctgt gcctgttctc tctcgcttgt 960

tcctcacaca cttgagaagg ccgaagctga ttcatagctt ggaaggcagg ggccttggat 1020

ttgaacccag gcctgaccaa tggcagaacc tatcagatgt gtggacagat gacattgcct 1080

ttctttcttt ggatatatca aaatcagcca gcaggcagga actcccattt tgagcaagca 1140

atgtgcagga atgatagggt atacagagag gaacaggaga tggcccctga cttccagcat 1200

gtgtctgatg gacatccagg ctgcaggcat catggtgctg tctagagaga tgagccaggt 1260

gcccagagcc catgggccaa tgctgccctt tcttgagcat gccaaacaaa gcggttggtg 1320

tgttagaggc acagtctcct ccactctaag taaaaatcag catgagtcct agcccacatt 1380

tccctagtga gtacaccaaa gatatctatg aactggcagt catcagtgac ttcctaaggt 1440

tccggaaatg catctcttac tcaggagtaa gcaatgatgt gcctgcggct ttacgagttc 1500

tcacagaatg actttctgga cccaaatgtt ttttctgctt caggactgtg aaggccttat 1560

tgttcgctct gccaccaagg tgaccgctga tgtcatcaac gcagctgaga aactccaggt 1620

ggtgggcagg gctggcacag gtgtggacaa tgtggatctg gaggccgcaa caaggaaggg 1680

catcttggtt atgaacaccc ccaatgggaa cagcctcagt gccgcagaac tcacttgtgg 1740

aatgatcatg tgcctggcca ggcagattcc ccaggcgacg gcttcgatga aggacggcaa 1800

atgggagcgg aagaagttca tgggaacaga gctgaatgga aagaccctgg gaattcttgg 1860

cctgggcagg attgggagag aggtagctac ccggatgcag tcctttggga tgaagactat 1920

agggtatgac cccatcattt ccccagaggt ctcggcctcc tttggtgttc agcagctgcc 1980

cctggaggag atctggcctc tctgtgattt catcactgtg cacactcctc tcctgccctc 2040

cacgacaggc ttgctgaatg acaacacctt tgcccagtgc aagaaggggg tgcgtgtggt 2100

gaactgtgcc cgtggaggga tcgtggacga aggcgccctg ctccgggccc tgcagtctgg 2160

ccagtgtgcc ggggctgcac tggacgtgtt tacggaagag ccgccacggg accgggcctt 2220

ggtggaccat gagaatgtca tcagctgtcc ccacctgggt gccagcacca aggaggctca 2280

gagccgctgt ggggaggaaa ttgctgttca gttcgtggac atggtgaagg ggaaatctct 2340

cacgggggtt gtgaatgccc aggcccttac cagtgccttc tctccacaca ccaagccttg 2400

gattggtctg gcagaagctc tggggacact gatgcgagcc tgggctgggt cccccaaagg 2460

gaccatccag gtgataacac agggaacatc cctgaagaat gctgggaact gcctaagccc 2520

cgcagtcatt gtcggcctcc tgaaagaggc ttccaagcag gcggatgtga acttggtgaa 2580

cgctaagctg ctggtgaaag aggctggcct caatgtcacc acctcccaca gccctgctgc 2640

accagggggg caaggcttcg gggaatgcct cctggccgtg gccctggcag gcgcccctta 2700

ccaggctgtg ggcttggtcc aaggcactac acctgtactg caggggctca atggagctgt 2760

cttcaggcca gaagtgcctc tccgcaggga cctgcccctg ctcctattcc ggactcagac 2820

ctctgaccct gcaatgctgc ctaccatgat tggcctcctg gcagaggcag gcgtgcggct 2880

gctgtcctac cagacttcac tggtgtcaga tggggagacc tggcacgtca tgggcatctc 2940

ctccttgctg cccagcctgg aagcgtggaa gcagcatgtg actgaagcct tccagttcca 3000

cttctaacct tggagctcac tggtccctgc ctctggggct tttctgaaga aacccaccca 3060

ctgtgatcaa tagggagaga aaatccacat tcttgggctg aacgcgagcc tctgacactg 3120

cttacactgc actctgaccc tgtagtacag caataaccgt ctaataaaga gcctaccccc 3180

<210> 145

<211> 1301

<212> DNA

<213>Homo sapiens

<220>

<221>Miscellaneous feature

<222> (1301)..(1301)

<223>N is a, c, g or t

<400> 145

caaacaaaaa cagccaagct tttctgccaa aaagatgact gagaagactg ttaaagcaaa 60

aagctctgtt cctgcctcag atgatgccta tccagaaata gaaaaattct ttcccttcaa 120

tcctctagac tttgagagtt ttgacctgcc tgaagagcac cagattgcgc acctcccctt 180

gagtggagtg cctctcatga tccttgacga ggagagagag cttgaaaagc tgtttcagct 240

gggcccccct tcacctgtga agatgccctc tccaccatgg gaatccaatc tgttgcagtc 300

tccttcaagc attctgtcga ccctggatgt tgaattgcca cctgtttgct gtgacataga 360

tatttaaatt tcttagtgct tcagagtctg tgtgtatttg tattaataaa gcattcttta 420

acagaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa agggggggga 480

gacacaaaaa gaattcccca agagggggcc acaagataat cagaggatat cacacaagat 540

ctctcggcgc accaacgacg ggggccccaa ataagggaga gacccagaat cacaacagcc 600

aagacacggt ggacacgacg gaaacaaaca cacagcccag acacgggggc aaacacgcgc 660

gcacaccgcg gacaccatgg gacaaagcag acaccaccca caaaacaaca ccgcggaggg 720

ggaagaacaa caaaacaagt gcgcaaacag aacacaacca cagaaagaga aaaattaaaa 780

cggcccccaa gacggcgaca acacaacaaa acaaccacta cagagcgctc aacagccgag 840

taaaaacaca acaacggaca actaacacac aaaggaatga aacaaagcgg ggccacacac 900

cgacaccgga aatccggcga acaactcaca ccgagcgagg gtcccagaca acaaatacac 960

agacaacgaa accgagaaac aagaccagca agacgagcag gcaaaagaca aacaagacag 1020

aggagacgac gacgaacgca aaggacaaga ggacacaacg acgcgaggag cgagagcgag 1080

aggaagagac aacaaaaaga cacaaaagaa caacaagcaa gcagcgaaga acgacacaca 1140

accacacgag acagcaggag cagaggcgga gaaaacacaa cgagcaagcc aagaccaaga 1200

gaggagaaca aaataaaaaa atacgagagc aggcggacga gagcacgaga cgaacagaca 1260

aacgggaatc agaagcataa cgatccgcga cgcgaacaac n 1301

<210> 146

<211> 3203

<212> DNA

<213>Homo sapiens

<400> 146

gtgcaccctg tcccagccgt cctgtcctgg ctgctcgctc tgcttcgctg cgcctccact 60

atgctctccc tccgtgtccc gctcgcgccc atcacggacc cgcagcagct gcagctctcg 120

ccgctgaagg ggctcagctt ggtcgacaag gagaacacgc cgccggccct gagcgggacc 180

cgcgtcctgg ccagcaagac cgcgaggagg atcttccagg agaaaacccc cgccgctttg 240

tcatcttccc catcgagtac catgatatct ggcagatgta taagaaggca gaggcttcct 300

tttggaccgc cgaggaggtg gacctctcca aggacattca gcactgggaa tccctgaaac 360

ccgaggagag atattttata tcccatgttc tggctttctt tgcagcaagc gatggcatag 420

taaatgaaaa cttggtggag cgatttagcc aagaagttca gattacagaa gcccgctgtt 480

tctatggctt ccaaattgcc atggaaaaca tacattctga aatgtatagt cttcttattg 540

acacttacat aaaagatccc aaagaaaggg aatttctctt caatgccatt gaaacgatgc 600

cttgtgtcaa gaagaaggca gactgggcct tgcgctggat tggggacaaa gaggctacct 660

atggtgaacg tgttgtagcc tttgctgcag tggaaggcat tttcttttcc ggttcttttg 720

cgtcgatatt ctggctcaag aaacgaggac tgatgcctgg cctcacattt tctaatgaac 780

ttattagcag agatgagggt ttacactgtg attttgcttg cctgatgttc aaacacctgg 840

tacacaaacc atcggaggag agagtaagag aaataattat caatgctgtt cggatagaac 900

aggagttcct cactgaggcc ttgcctgtga agctcattgg gatgaattgc actctaatga 960

agcaatacat tgagtttgtg gcagacagac ttatgctgga actgggtttt agcaaggttt 1020

tcagagtaga gaacccattt gactttatgg agaatatttc actggaagga aagactaact 1080

tctttgagaa gagagtaggc gagtatcaga ggatgggagt gatgtcaagt ccaacagaga 1140

attcttttac cttggatgct gacttctaaa tgaactgaag atgtgccctt acttggctga 1200

tttttttttt tccatctcat aagaaaaatc agctgaagtg ttaccaacta gccacaccat 1260

gaattgtccg taatgttcat taacagcatc tttaaaactg tgtagctacc tcacaaccag 1320

tcctgtctgt ttatagtgct ggtagtatca ccttttgcca gaaggcctgg ctggctgtga 1380

cttaccatag cagtgacaat ggcagtcttg gctttaaagt gaggggtgac cctttagtga 1440

gcttagcaca gcgggattaa acagtccttt aaccagcaca gccagttaaa agatgcagcc 1500

tcactgcttc aacgcagatt ttaatgttta cttaaatata aacctggcac tttacaaaca 1560

aataaacatt gtttgtactc acaaggcgat aatagcttga tttatttggt ttctacacca 1620

aatacattct cctgaccact aatgggagcc aattcacaat tcactaagtg actaaagtaa 1680

gttaaacttg tgtagactaa gcatgtaatt tttaagtttt attttaatga attaaaatat 1740

ttgttaacca actttaaagt cagtcctgtg tatacctaga tattagtcag ttggtgccag 1800

atagaagaca ggttgtgttt ttatcctgtg gcttgtgtag tgtcctggga ttctctgccc 1860

cctctgagta gagtgttgtg ggataaagga atctctcagg gcaaggagct tcttaagtta 1920

aatcactaga aatttagggg tgatctgggc cttcatatgt gtgagaagcc gtttcatttt 1980

atttctcact gtattttcct caacgtctgg ttgatgagaa aaaattcttg aagagttttc 2040

atatgtggga gctaaggtag tattgtaaaa tttcaagtca tccttaaaca aaatgatcca 2100

cctaagatct tgcccctgtt aagtggtgaa atcaactaga ggtggttcct acaagttgtt 2160

cattctagtt ttgtttggtg taagtaggtt gtgtgagtta attcatttat atttactatg 2220

tctgttaaat cagaaatttt ttattatcta tgttcttcta gattttacct gtagttcata 2280

cttcagtcac ccagtgtctt attctggcat tgtctaaatc tgagcattgt ctagggggat 2340

cttaaacttt agtaggaaac catgagctgt taatacagtt tccattcaaa tattaatttc 2400

agaatgaaac ataatttttt tttttttttt ttgagatgga gtctcgctct gttgcccagg 2460

ctggagtgca gtggcgcgat tttggctcac tgtaacctcc atctcctggg ttcaagcaat 2520

tctcctgtct cagcctccct agtagctggg actgcaggta tgtgctacca cacctggcta 2580

atttttgtat ttttagtaga gatggagttt caccatattg gtcaggctgg tcttgaactc 2640

ctgacctcag gtgatccacc cacctcggcc tcccaaagtg ctgggattgc aggcgtgata 2700

aacaaatatt cttaataggg ctactttgaa ttaatctgcc tttatgtttg ggagaagaaa 2760

gctgagacat tgcatgaaag atgatgagag ataaatgttg atcttttggc cccatttgtt 2820

aattgtattc agtatttgaa cgtcgtcctg tttattgtta gttttcttca tcatttattg 2880

tatagacaat ttttaaatct ctgtaatatg atacattttc ctatctttta agttattgtt 2940

acctaaagtt aatccagatt atatggtcct tatatgtgta caacattaaa atgaaaggct 3000

ttgtcttgca ttgtgaggta caggcggaag ttggaatcag gttttaggat tctgtctctc 3060

attagctgaa taatgtgagg attaacttct gccagctcag accatttcct aatcagttga 3120

aagggaaaca agtatttcag tctcaaaatt gaataatgca caagtcttaa gtgattaaaa 3180

taaaactgtt cttatgtcag ttt 3203

<210> 147

<211> 4482

<212> DNA

<213>Homo sapiens

<400> 147

agcgggggca ctccagccct gcagcctccg gagtcagtgc cgcgcgcccg ccgccccgcg 60

ccttcctgct cgccgcacct ccgggagccg gggcgcaccc agcccgcagc gccgcctccc 120

cgcccgcgcc gcctccgacc gcaggccgag ggccgccact ggccgggggg accgggcagc 180

agcttgcggc cgcggagccg ggcaacgctg gggactgcgc cttttgtccc cggaggtccc 240

tggaagtttg cggcaggacg cgcgcgggga ggcggcggag gcagccccga cgtcgcggag 300

aacagggcgc agagccggca tgggcatcgg gcgcagcgag gggggccgcc gcggggcagc 360

cctgggcgtg ctgctggcgc tgggcgcggc gcttctggcc gtgggctcgg ccagcgagta 420

cgactacgtg agcttccagt cggacatcgg cccgtaccag agcgggcgct tctacaccaa 480

gccacctcag tgcgtggaca tccccgcgga cctgcggctg tgccacaacg tgggctacaa 540

gaagatggtg ctgcccaacc tgctggagca cgagaccatg gcggaggtga agcagcaggc 600

cagcagctgg gtgcccctgc tcaacaagaa ctgccacgcc ggcacccagg tcttcctctg 660

ctcgctcttc gcgcccgtct gcctggaccg gcccatctac ccgtgtcgct ggctctgcga 720

ggccgtgcgc gactcgtgcg agccggtcat gcagttcttc ggcttctact ggcccgagat 780

gcttaagtgt gacaagttcc ccgaggggga cgtctgcatc gccatgacgc cgcccaatgc 840

caccgaagcc tccaagcccc aaggcacaac ggtgtgtcct ccctgtgaca acgagttgaa 900

atctgaggcc atcattgaac atctctgtgc cagcgagttt gcactgagga tgaaaataaa 960

agaagtgaaa aaagaaaatg gcgacaagaa gattgtcccc aagaagaaga agcccctgaa 1020

gttggggccc atcaagaaga aggacctgaa gaagcttgtg ctgtacctga agaatggggc 1080

tgactgtccc tgccaccagc tggacaacct cagccaccac ttcctcatca tgggccgcaa 1140

ggtgaagagc cagtacttgc tgacggccat ccacaagtgg gacaagaaaa acaaggagtt 1200

caaaaacttc atgaagaaaa tgaaaaacca tgagtgcccc acctttcagt ccgtgtttaa 1260

gtgattctcc cgggggcagg gtggggaggg agcctcgggt ggggtgggag cgggggggac 1320

agtgccccgg gaacccggtg ggtcacacac acgcactgcg cctgtcagta gtggacattt 1380

aatccagtcg gcttgttctt gcagcattcc cgctcccttc cctccatagc cacgctccaa 1440

accccagggt agccatggcc gggtaaagca agggccattt agattaggaa ggtttttaag 1500

atccgcaatg tggagcagca gccactgcac aggaggaggt gacaaaccat ttccaacagc 1560

aacacagcca ctaaaacaca aaaaggggga ttgggcggaa agtgagagcc agcagcaaaa 1620

actacatttt gcaacttgtt ggtgtggatc tattggctga tctatgcctt tcaactagaa 1680

aattctaatg attggcaagt cacgttgttt tcaggtccag agtagtttct ttctgtctgc 1740

tttaaatgga aacagactca taccacactt acaattaagg tcaagcccag aaagtgataa 1800

gtgcagggag gaaaagtgca agtccattat gtaatagtga cagcaaaggg accaggggag 1860

aggcattgcc ttctctgccc acagtctttc cgtgtgattg tctttgaatc tgaatcagcc 1920

agtctcagat gccccaaagt ttcggttcct atgagcccgg ggcatgatct gatccccaag 1980

acatgtggag gggcagcctg tgcctgcctt tgtgtcagaa aaaggaaacc acagtgagcc 2040

tgagagagac ggcgattttc gggctgagaa ggcagtagtt ttcaaaacac atagttaaaa 2100

aagaaacaaa tgaaaaaaat tttagaacag tccagcaaat tgctagtcag ggtgaattgt 2160

gaaattgggt gaagagctta cgattctaat ctcatgtttt ttccttttca catttttaaa 2220

agaacaatga caaacaccca cttatttttc aaggttttaa aacagtctac attgagcatt 2280

tgaaaggtgt gctagaacaa ggtctcctga tccgtccgag gctgcttccc agaggagcag 2340

ctctccccag gcatttgcca agggaggcgg atttccctgg tagtgtagct gtgtggcttt 2400

ccttcctgaa gagtccgtgg ttgccctaga acctaacacc ccctagcaaa actcacagag 2460

ctttccgttt ttttctttcc tgtaaagaaa catttccttt gaacttgatt gcctatggat 2520

caaagaaatt cagaacagcc tgcctgtccc cccgcacttt ttacatatat ttgtttcatt 2580

tctgcagatg gaaagttgac atgggtgggg tgtccccatc cagcgagaga gtttaaaaag 2640

caaaacatct ctgcagtttt tcccaagtgc cctgagatac ttcccaaagc ccttatgttt 2700

aatcagcgat gtatataagc cagttcactt agacaacttt acccttcttg tccaatgtac 2760

aggaagtagt tctaaaaaaa atgcatatta atttcttccc ccaaagccgg attcttaatt 2820

ctctgcaaca ctttgaggac atttatgatt gtccctctgg gccaatgctt atacccagtg 2880

aggatgctgc agtgaggctg taaagtggcc ccctgcggcc ctagcctgac ccggaggaaa 2940

ggatggtaga ttctgttaac tcttgaagac tccagtatga aaatcagcat gcccgcctag 3000

ttacctaccg gagagttatc ctgataaatt aacctctcac agttagtgat cctgtccttt 3060

taacaccttt tttgtggggt tctctctgac ctttcatcgt aaagtgctgg ggaccttaag 3120

tgatttgcct gtaattttgg atgattaaaa aatgtgtata tatattagct aattagaaat 3180

attctacttc tctgttgtca aactgaaatt cagagcaagt tcctgagtgc gtggatctgg 3240

gtcttagttc tggttgattc actcaagagt tcagtgctca tacgtatctg ctcattttga 3300

caaagtgcct catgcaaccg ggccctctct ctgcggcaga gtccttagtg gaggggttta 3360

cctggaacat tagtagttac cacagaatac ggaagagcag gtgactgtgc tgtgcagctc 3420

tctaaatggg aattctcagg taggaagcaa cagcttcaga aagagctcaa aataaattgg 3480

aaatgtgaat cgcagctgtg ggttttacca ccgtctgtct cagagtccca ggaccttgag 3540

tgtcattagt tactttattg aaggttttag acccatagca gctttgtctc tgtcacatca 3600

gcaatttcag aaccaaaagg gaggctctct gtaggcacag agctgcacta tcacgagcct 3660

ttgtttttct ccacaaagta tctaacaaaa ccaatgtgca gactgattgg cctggtcatt 3720

ggtctccgag agaggaggtt tgcctgtgat ttcctaatta tcgctagggc caaggtggga 3780

tttgtaaagc tttacaataa tcattctgga tagagtcctg ggaggtcctt ggcagaactc 3840

agttaaatct ttgaagaata tttgtagtta tcttagaaga tagcatggga ggtgaggatt 3900

ccaaaaacat tttattttta aaatatcctg tgtaacactt ggctcttggt acctgtgggt 3960

tagcatcaag ttctccccag ggtagaattc aatcagagct ccagtttgca tttggatgtg 4020

taaattacag taatcccatt tcccaaacct aaaatctgtt tttctcatca gactctgagt 4080

aactggttgc tgtgtcataa cttcatagat gcaggaggct caggtgatct gtttgagcag 4140

agcaccctag gcagcctgca gggaataaca tactggccgt tctgacctgt tgccagcaga 4200

tacacaggac atggatgaaa ttcccgtttc ctctagtttc ttcctgtagt actcctcttt 4260

tagatcctaa gtctcttaca aaagctttga atactgtgaa aatgttttac attccatttc 4320

atttgtgttg tttttttaac tgcattttac cagatgtttt gatgttatcg cttatgttaa 4380

tagtaattcc cgtacgtgtt cattttattt tcatgctttt tcagccatgt atcaatattc 4440

acttgactaa aatcactcaa ttaatcaaaa aaaaaaaaaa aa 4482

<210> 148

<211> 3637

<212> DNA

<213>Homo sapiens

<400> 148

agtcctgggc gaagggggcg gtggttcccc gcggcgctgc gcgcggcggt aattagtgat 60

tgtcttccag cttcgcgaag gctaggggcg cggctgccgg gtggctgcgc ggcgctgccc 120

ccggaccgag gggcagccaa cccaatgaaa ccaccgcgtg ttcgcgcctg gtagagattt 180

ctcgaagaca ccagtgggcc cgttccgagc cctctggacc gcccgtgtgg aaccaaacct 240

gcgcgcgtgg ccgggccgtg ggacaacgag gccgcggaga cgaaggcgca atggcgagga 300

agttatctgt aatcttgatc ctgacctttg ccctctctgt cacaaatccc cttcatgaac 360

taaaagcagc tgctttcccc cagaccactg agaaaattag tccgaattgg gaatctggca 420

ttaatgttga cttggcaatt tccacacggc aatatcatct acaacagctt ttctaccgct 480

atggagaaaa taattctttg tcagttgaag ggttcagaaa attacttcaa aatataggca 540

tagataagat taaaagaatc catatacacc atgaccacga ccatcactca gaccacgagc 600

atcactcaga ccatgagcgt cactcagacc atgagcatca ctcagaccac gagcatcact 660

ctgaccatga tcatcactct caccataatc atgctgcttc tggtaaaaat aagcgaaaag 720

ctctttgccc agaccatgac tcagatagtt caggtaaaga tcctagaaac agccagggga 780

aaggagctca ccgaccagaa catgccagtg gtagaaggaa tgtcaaggac agtgttagtg 840

ctagtgaagt gacctcaact gtgtacaaca ctgtctctga aggaactcac tttctagaga 900

caatagagac tccaagacct ggaaaactct tccccaaaga tgtaagcagc tccactccac 960

ccagtgtcac atcaaagagc cgggtgagcc ggctggctgg taggaaaaca aatgaatctg 1020

tgagtgagcc ccgaaaaggc tttatgtatt ccagaaacac aaatgaaaat cctcaggagt 1080

gtttcaatgc atcaaagcta ctgacatctc atggcatggg catccaggtt ccgctgaatg 1140

caacagagtt caactatctc tgtccagcca tcatcaacca aattgatgct agatcttgtc 1200

tgattcatac aagtgaaaag aaggctgaaa tccctccaaa gacctattca ttacaaatag 1260

cctgggttgg tggttttata gccatttcca tcatcagttt cctgtctctg ctgggggtta 1320

tcttagtgcc tctcatgaat cgggtgtttt tcaaatttct cctgagtttc cttgtggcac 1380

tggccgttgg gactttgagt ggtgatgctt ttttacacct tcttccacat tctcatgcaa 1440

gtcaccacca tagtcatagc catgaagaac cagcaatgga aatgaaaaga ggaccacttt 1500

tcagtcatct gtcttctcaa aacatagaag aaagtgccta ttttgattcc acgtggaagg 1560

gtctaacagc tctaggaggc ctgtatttca tgtttcttgt tgaacatgtc ctcacattga 1620

tcaaacaatt taaagataag aagaaaaaga atcagaagaa acctgaaaat gatgatgatg 1680

tggagattaa gaagcagttg tccaagtatg aatctcaact ttcaacaaat gaggagaaag 1740

tagatacaga tgatcgaact gaaggctatt tacgagcaga ctcacaagag ccctcccact 1800

ttgattctca gcagcctgca gtcttggaag aagaagaggt catgatagct catgctcatc 1860

cacaggaagt ctacaatgaa tatgtaccca gagggtgcaa gaataaatgc cattcacatt 1920

tccacgatac actcggccag tcagacgatc tcattcacca ccatcatgac taccatcata 1980

ttctccatca tcaccaccac caaaaccacc atcctcacag tcacagccag cgctactctc 2040

gggaggagct gaaagatgcc ggcgtcgcca ctctggcctg gatggtgata atgggtgatg 2100

gcctgcacaa tttcagcgat ggcctagcaa ttggtgctgc ttttactgaa ggcttatcaa 2160

gtggtttaag tacttctgtt gctgtgttct gtcatgagtt gcctcatgaa ttaggtgact 2220

ttgctgttct actaaaggct ggcatgaccg ttaagcaggc tgtcctttat aatgcattgt 2280

cagccatgct ggcgtatctt ggaatggcaa caggaatttt cattggtcat tatgctgaaa 2340

atgtttctat gtggatattt gcacttactg ctggcttatt catgtatgtt gctctggttg 2400

atatggtacc tgaaatgctg cacaatgatg ctagtgacca tggatgtagc cgctgggggt 2460

atttcttttt acagaatgct gggatgcttt tgggttttgg aattatgtta cttatttcca 2520

tatttgaaca taaaatcgtg tttcgtataa atttctagtt aaggtttaaa tgctagagta 2580

gcttaaaaag ttgtcatagt ttcagtaggt catagggaga tgagtttgta tgctgtacta 2640

tgcagcgttt aaagttagtg ggttttgtga tttttgtatt gaatattgct gtctgttaca 2700

aagtcagtta aaggtacgtt ttaatattta agttattcta tcttggagat aaaatctgta 2760

tgtgcaattc accggtatta ccagtttatt atgtaaacaa gagatttggc atgacatgtt 2820

ctgtatgttt cagggaaaaa tgtctttaat gctttttcaa gaactaacac agttattcct 2880

atactggatt ttaggtctct gaagaactgc tggtgtttag gaataagaat gtgcatgaag 2940

cctaaaatac caagaaagct tatactgaat ttaagcaaag aaataaagga gaaaagagaa 3000

gaatctgaga attggggagg catagattct tataaaaatc acaaaatttg ttgtaaatta 3060

gaggggagaa atttagaatt aagtataaaa aggcagaatt agtatagagt acattcatta 3120

aacatttttg tcaggattat ttcccgtaaa aacgtagtga gcacttttca tatactaatt 3180

tagttgtaca tttaactttg tataatacag aaatctaaat atatttaatg aattcaagca 3240

atatatcact tgaccaagaa attggaattt caaaatgttc gtgcgggtat ataccagatg 3300

agtacagtga gtagttttat gtatcaccag actgggttat tgccaagtta tatatcacca 3360

aaagctgtat gactggatgt tctggttacc tggtttacaa aattatcaga gtagtaaaac 3420

tttgatatat atgaggatat taaaactaca ctaagtatca tttgattcga ttcagaaagt 3480

actttgatat ctctcagtgc ttcagtgcta tcattgtgag caattgtctt ttatatacgg 3540

tactgtagcc atactaggcc tgtctgtggc attctctaga tgtttctttt ttacacaata 3600

aattccttat atcagcttga aaaaaaaaaa aaaaaaa 3637

<210> 149

<211> 2208

<212> DNA

<213>Homo sapiens

<400> 149

aacgcacttg gcgcgcggcg cgggctgcag acggctgcga ggcgctgggc acaggtgtcc 60

tgatggcaaa tttcaagggc cacgcgcttc cagggagttt cttcctgatc attgggctgt 120

gttggtcagt gaagtacccg ctgaagtact ttagccacac gcggaagaac agcccactac 180

attactatca gcgtctcgag atcgtcgaag ccgcaattag gactttgttt tccgtcactg 240

ggatcctggc agagcagttt gttccggatg ggccccacct gcacctctac catgagaacc 300

actggataaa gttaatgaat tggcagcaca gcaccatgta cctattcttt gcagtctcag 360

gaattgttga catgctcacc tatctggtca gccacgttcc cttgggggtg gacagactgg 420

ttatggctgt ggcagtattc atggaaggtt tcctcttcta ctaccacgtc cacaaccggc 480

ctccgctgga ccagcacatc cactcactcc tgctgtatgc tctgttcgga gggtgtgtta 540

gtatctccct agaggtgatc ttccgggacc acattgtgct ggaacttttc cgaaccagtc 600

tcatcattct tcagggaacc tggttctggc agattgggtt tgtgctgttc ccaccttttg 660

gaacacccga atgggaccag aaggatgatg ccaacctcat gttcatcacc atgtgcttct 720

gctggcacta cctggctgcc ctcagcattg tggccgtcaa ctattctctt gtttactgcc 780

ttttgactcg gatgaagaga cacggaaggg gagaaatcat tggaattcag aagctgaatt 840

cagatgacac ttaccagacc gccctcttga gtggctcaga tgaggaatga gccgagatgc 900

ggagggcgca gatgtcccac tgcacagctg gaatgaatgg agttcatccc ctccacctga 960

atgcctgctg tggtctgatc ttaagggtct atatatttgc acctcctcat tcaacacagg 1020

gctggaggtt ctacaacagg aaatcaggcc tacagcatcc tgtgtatctt gcagttggga 1080

tttttaaaca tactataaag tctgtgttgg tatagtaccc ttcataagga aaaatgaagt 1140

aatgcctata agtagcaggc ctttgtgcct cagtgtcaag agaaatcaag agatgctaaa 1200

agctttacaa tggaagtggc ctcatggatg aatccggggt atgagcccag gagaacgtgc 1260

tgcttttggt aacttatccc tttttctctt aagaaagcag gtactttctt attagaaata 1320

tgttagaatg tgtaagcaaa cgacagtgcc tttagaatta caattctaac ttacatattt 1380

tttgaaagta aaataattca caagctttgg tattttaaaa ttattgttaa acatatcata 1440

actaatcata ccagggtact gcaataccac tgtttataag tgacaaaatt aggccaaagg 1500

tgattttttt ttaaatcagg aagctggtta ctggctctac tgagagttgg agccctgatg 1560

ttctgattct tcaaagtcac cctaaaagaa gatctgacag gaaagctgta taatgagata 1620

gaaaaacgtc aggtatggaa ggctttcagt tttaatatgg ctgaaagcaa aggataacga 1680

attcagaatt agtaatgtaa aatcttgata ccctaatctt gcttctggat ctgttctttt 1740

tttaaaaaaa cttccttcac cgcgcctata atcctagcac tttgggaggc cgaggcaggc 1800

agatcacggg gtcaggagat caagaccatc ctggctaaca tggtgaaacc ccgtctctac 1860

tgaaaataca aaaaattagc cgggtgtggt ggcgggcgcc tgtagttcca gctactcggg 1920

aggctgaggc aagagaatgg catgaacccg gtaggggagc ttgcagtgag cccagatcat 1980

gccactgtac tccagcctag gtgacagagc aagactctgt ctcaaaaaca agcaaacaga 2040

cttccttcaa caaatattta ttaaatatcc actttgcaac agcactgaaa tggctgtaag 2100

gactcctgag atatgtgtcc agcaaggagt ttacagtcaa acaggagaga catgcctgta 2160

gttacatcca gtgtgatggg tgctgagagg caagtacaaa ccacgatg 2208

<210> 150

<211> 1678

<212> DNA

<213>Homo sapiens

<220>

<221>Miscellaneous feature

<222> (523)..(523)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (569)..(569)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (961)..(961)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1021)..(1021)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1066)..(1066)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1069)..(1069)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1194)..(1194)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1202)..(1202)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1287)..(1287)

<223>N is a, c, g or t

<220>

<221>Miscellaneous feature

<222> (1472)..(1472)

<223>N is a, c, g or t

<400> 150

tcccgccgcg ccacttcgcc tgcctccgtc ccccgcccgc cgcgccatgc ctgtggccgg 60

ctcggagctg ccgcgccggc ccttgccccc cgccgcacag gagcgggacg ccgagccgcg 120

tccgccgcac ggggagctgc agtacctggg gcagatccaa cacatcctcc gctgcggcgt 180

caggaaggac gcccgcccgg gcaccggtac cctgccggta ttcggcatgc aggcgcgcta 240

cagcctgaga gatgaattcc ctctgctgac aaccaaacgt gtgttctgga acggtgcttc 300

ggaggagctg ctgtggctta tcaagggatc cacaaacgct atagacctgt cttccccggc 360

agcgaaaatc tcgggatgcc actggatccc gacactctct ggacaccctg ggattctcca 420

ccagagaaga acgcgacttg ggcccagttt gtggctctca gcggaggcct cctgtggcag 480

aatacataca tttccaatca gatcacttcc cggacacgga ccntgaccag cctgccaaaa 540

agtggatttc cccccacccc agaacccanc ccctgacgca cagaaaccaa cccattcgtt 600

gttgccgcct tgcgaacccc aaccagaatc tctcccccct ggccggcgcg cctgccgctg 660

ccaatgcccc tatggcggcc tcttggcccg caccttccaa ttggtcgccc tgcgcaacca 720

gcgagaaaac actggcccgc ccgtctcccc cccgctccgc ctaccccact taatgcgcct 780

ccgtggcatg acgcacgcgt ttggtgtccg ccgccgtctc atgtccgcgc ggtgtggacc 840

cccttttctc tcgcggcaca tcccccctat tcccttgccc tttggggggc accccctcta 900

gacccgcgct tctcttctcg tccggtgggg gacattggtt tgcctgccgc ggcgggggcg 960

ntaaaaataa aaacagcctg ttagcccggc ccagtacccc cccccggccg gggccgcctt 1020

ncgtttgcat ttatacccca acccataaag ccgcgcccct ttagcnccnt aacttttgtg 1080

gtgtggcctc cccccttttt cccggggagc agcaacggac atctgtacac taatgctggc 1140

cccgaccttt cccaaaaacc ccccgcccgt gtcccgtata aatttggtgc caancctgac 1200

gngttctccc ccgccctcgc cccgttggcc gcccgtttaa agcccccccg gtggttgcgc 1260

cgcccaacga gtccacctat agttaantcc accaacaccc ccaccttttc ctccccgccg 1320

catcttcccc acgtaccccc ttttgtcgcg agatggccac tccccccccc ctgtttgttt 1380

aaaacaacga gaatggtgct gccaacgctg gtcttttccc cccccggacc gcgaccgcca 1440

gggggaatac gtaccataag cccccgcgcc cncctttttt cccccctccc cgccaatcaa 1500

gatccgccgt ccattagacg tattattttt cccgcgatac acgaaaaaac agggccgccc 1560

atttataact aaattcccgt cgccgccgcg cggatatgtt tcccaaaata ccaccccccc 1620

ccccccattt tctttgcccc caactcctgc gcaccggtgt tcaccagcct cgcgccgc 1678

<210> 151

<211> 1611

<212> DNA

<213>Homo sapiens

<400> 151

ggacgcgtgg gtcgacccac gcgtccggac ccacgcgtcc ggtcgtgttc tccgagttcc 60

tgtctctctg ccaacgccgc ccggatggct tcccaaaacc gcgacccagc cgccactagc 120

gtcgccgccg cccgtaaagg agctgagccg agcgggggcg ccgcccgggg tccggtgggc 180

aaaaggctac agcaggagct gatgaccctc atggtgagtg attaagtgcc cagaacccca 240

gccttccatc caattttcag tagcctcctt ttttccgtca gcttttttgc tagacatagg 300

ggtaatgtaa tttgctccct cctgggaaag aagttcatac accccaccta caccatttct 360

tccagcagtc cctcctccca attccatccc cccacacgaa gttatctcga acacttccct 420

gaagtcatac aagaccctcc ctatccagtg tgtccctact tcctagcccc aaccaagctt 480

tacccacacc caactccccg cccttcttgg tatttctagc ctatgaattt ggttgcttta 540

ttttggatca gagtgatgag attaagggga ggctgggcgc ggtagctcac accttataat 600

cccaaagtgc tgggattaca ggcgtgagcc accgcgcccg gccagcaact aatattctaa 660

ttgaactaaa gcacaggatg ccaatttaca atccttagac caaagagtca ctgatgtctc 720

caccagataa gaggaaagca tcaggctagg catagtggct cacacctgta atctcagcac 780

tttgggaggc tgaggcaggc agatcacatg agcccaggag tttgagactg gcctgggcaa 840

catggtgaaa ccctgtctct aaaataaaaa ctaaactaaa aaaacttttt aaaaaggcag 900

tggggagcat cagaaccagc tcaacagttt gtctactgtc cggtcccaga gaaactcaag 960

attctagcaa gccccttgtg tggggcttgg gttgggacat gaggctgctg ctggagctta 1020

ctctgcaact gtttctccaa atgccaggta tatgaagacc tgaggtataa gctctcgcta 1080

gagttcccca gtggctaccc ttacaatgcg cccacagtga agttcctcac gccctgctat 1140

caccccaacg tggacaccca gggtaacata tgcctggaca tcctgaagga aaagtggtct 1200

gccctgtatg atgtcaggac cattctgctc tccatccaga gccttctagg agaacccaac 1260

attgatagtc ccttgaacac acatgctgcc gagctctgga aaaaccccac agcttttaag 1320

aagtacctgc aagaaaccta ctcaaagcag gtcaccagcc aggagccctg acccaggctg 1380

cccagcctgt ccttgtgtcg tctttttaat ttttccttag atggtctgtc ctttttgtga 1440

tttctgtata ggactcttta tcttgagctg tggtattttt gttttgtttt tgtcttttaa 1500

attaagcctc ggttgagccc ttgtatatta aataaatgca tttttgtcct tttttaaaaa 1560

aaaaataaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1611

Claims

1. screening the method for the treatment for triple negative breast cancer, the treatment is described comprising androgen receptor inhibitor is used Method includes determining the biological sample obtained from subject, to determine whether the biological sample obtained from subject is classified as base Original pattern hypotype or another hypotype.

2. according to the method described in claim 1, wherein determining the biological sample to determine whether the biological sample is divided Class is that substrate sample hypotype or another hypotype are carried out by detecting the expression of the intrinsic gene set shown in table 1.

3. method according to claim 2, including：

(a) the substrate barycenter grader score of sample is determined from the expression of the intrinsic gene set shown in table 1；

(b) the tube chamber A barycenter grader scores of sample are determined from the expression of the intrinsic gene set shown in table 1；With

(c) substrate of weighting is calculated from substrate barycenter grader score and tube chamber A barycenter graders score according to following equation With tube chamber A grader scores：

(tube chamber A barycenter is classified for the substrate of weighting and tube chamber A graders score=- 0.25 (substrate barycenter grader score)+0.27 Device score)

If the substrate and tube chamber A graders score of wherein weighting are more than -0.3, obtained with the substrate and tube chamber A graders of weighting Divide and compared less than or equal to -0.3, the breast cancer treatment comprising androgen receptor inhibitor is more likely effective in subject 's.

4. method according to claim 3, if wherein the substrate and tube chamber A graders score of weighting are more than -0.2, Compared with the substrate and tube chamber A graders score of weighting are less than or equal to -0.2, include the breast cancer of androgen receptor inhibitor Treatment is more likely effective in subject.

5. method according to claim 4, if wherein the substrate and tube chamber A graders score of weighting are more than -0.25, Compared with the substrate and tube chamber A graders score of weighting are less than or equal to -0.25, the breast cancer comprising androgen receptor inhibitor Treatment is more likely effective in subject.

6. method according to claim 2, includes the substrate matter of the expression determination sample from the intrinsic gene set shown in table 1 Heart grader score, if wherein substrate barycenter grader score be less than or equal to 0.9, it is big with substrate barycenter grader score Compared in 0.9, the breast cancer treatment comprising androgen receptor inhibitor is more likely effective when treating subject.

7. method according to claim 6, if wherein the substrate barycenter grader score is less than or equal to 0.6, Breast cancer treatment comprising androgen receptor inhibitor is probably effective when treating subject.

8. method according to claim 6, if wherein scope of the substrate barycenter grader score 0.2 to 0.8 Interior, then the breast cancer treatment comprising androgen receptor inhibitor is probably effective when treating subject.

9. method according to claim 8, if wherein scope of the substrate barycenter grader score 0.4 to 0.7 Interior, then the breast cancer treatment comprising androgen receptor inhibitor is probably effective when treating subject.

10. method according to any one of claim 1 to 9, wherein the breast cancer of the subject is characterised by male The presence of hormone receptor positive tumors cell.

11. method according to any one of claim 1 to 10, wherein the biological sample is selected from cell, tissue and body Liquid.

12. method according to claim 11, wherein the biological sample includes breast tissue or cell.

13. method according to claim 11, wherein the tissue is obtained from biopsy.

14. method according to claim 11, wherein the body fluid is selected from blood, lymph, urine, saliva, from conduit The liquid of irrigating solution, and nipple aspirate.

15. androgen receptor inhibitor, it is used to treat the triple negative breast cancer in subject, wherein it has been determined that from institute The biological sample of subject is stated to determine whether sample is classified as substrate sample hypotype or another hypotype.

16. the purposes of inhibitor according to claim 15, wherein determining the biological sample to determine the biological sample Whether product are classified as substrate sample hypotype or another hypotype by the expression of the intrinsic gene shown in detection table 1 to carry out.

17. the purposes of inhibitor according to claim 16, including the expression of the intrinsic gene set shown in table 1 are determined The substrate barycenter grader score and tube chamber A barycenter grader scores of sample, and classified according to following equation from substrate barycenter Device score and tube chamber A barycenter graders score calculate the substrate and tube chamber A grader scores of weighting：

If the substrate and tube chamber A graders score of wherein weighting are more than -0.3, breast cancer treatment is applied to subject.

18. the purposes of inhibitor according to claim 17, if wherein the substrate and tube chamber A grader scores of weighting are big In -0.2, then using breast cancer treatment.

19. the purposes of inhibitor according to claim 18, if wherein the substrate and tube chamber A grader scores of weighting are big In -0.25, then using breast cancer treatment.

20. the purposes of inhibitor according to claim 16, including determine sample from the expression of the intrinsic gene set shown in table 1 The substrate barycenter grader score of product, if wherein substrate barycenter grader score is less than or equal to 0.9, administration breast cancer is controlled Treat.

21. the purposes of inhibitor according to claim 20, if wherein substrate barycenter grader score is less than or equal to 0.6, then using breast cancer treatment.

22. the purposes of inhibitor according to claim 20, wherein, if substrate barycenter grader score is 0.2 to 0.8 In the range of, then using breast cancer treatment.

23. the purposes of inhibitor according to claim 22, if wherein substrate barycenter grader score is 0.4 to 0.7 In the range of, then using breast cancer treatment.

24. the purposes of the inhibitor according to any one of claim 15 to 23, wherein the breast cancer of the subject It is characterised by the presence of androgen receptor positive tumor cell.

25. the purposes of the inhibitor according to any one of claim 15 to 24, wherein the androgen receptor inhibitor It is selected from：The miscellaneous Shandong amine of grace, Bicalutamide, Flutamide, Nilutamide, ARN509, ketoconazole, abiraterone acetate, VN/124-1 (TOK-001), orteronel (TAK-700), Finasteride, galeterone, CPA, andarine, Yi Jiqi Combination.

26. the purposes of inhibitor according to claim 25, wherein the androgen receptor inhibitor is the miscellaneous Shandong amine of grace.

27. the purposes of inhibitor according to claim 26, wherein the miscellaneous Shandong amine of the grace is oral daily once, dosage is 160mg。

28. the purposes of inhibitor according to claim 27, wherein the miscellaneous Shandong amine of the grace is as including the miscellaneous Shandong amine of 160mg grace Single capsule apply.

29. the purposes of inhibitor according to claim 27, wherein the miscellaneous Shandong amine of the grace is applied in the form of four capsules, Each capsule includes the miscellaneous Shandong amine of 40mg grace.

30. the purposes of the inhibitor according to any one of claim 15 to 29, wherein including androgen receptor inhibitor Breast cancer treatment also comprising one or more be not androgen receptor inhibitor other anticancers.

31. the purposes of inhibitor according to claim 30, suppresses wherein the one or more are not androgen receptors Other anticancers of agent are selected from endoxan, fluorouracil, 5 FU 5 fluorouracil, methotrexate (MTX), thiotepa, carboplatin, cis-platinum, Japanese yew Alkane, taxol, the taxol that protein is combined, docetaxel, vinorelbine, TAM, Raloxifene, Toremifene, fluorine Dimension department group, gemcitabine, Irinotecan, Ipsapirone, Temozolomide, TPT, vincristine, vinblastine, Ai Bu Woods, mutamycin, capecitabine, capecitabine, Anastrozole, Exemestane, Letrozole, Leuprorelin, abarelix, Bath Woods, Goserelin, megestrol acetate, Risedronate, Pamidronate, ibandronate, Alendronate, ground promise list Resist, zoledronate, Herceptin, Lapatinib or Avastin, with and combinations thereof.

32. purposes according to claim 31, wherein described is not that other anticancers of androgen receptor inhibitor are purple China fir alcohol.

33. the purposes of the inhibitor according to any one of claim 15 to 32, wherein the biological sample be selected from cell, Tissue and body fluid.

34. the purposes of inhibitor according to claim 33, wherein the biological sample includes breast tissue or cell.

35. the purposes of inhibitor according to claim 33, wherein the tissue is obtained from biopsy.

36. the purposes of inhibitor according to claim 33, wherein the body fluid be selected from blood, lymph, urine, saliva, Liquid from ductal lavage fluid, and nipple aspirate.

37. treating the method for the triple negative breast cancer in subject, the subject has comprising having been classified as not being base The breast cancer of the breast cancer cell of original pattern hypotype, methods described includes applying the breast comprising androgen receptor inhibitor to subject Gland cancer is treated, so as to treat the triple negative breast cancer in subject.

38. the method according to claim 37, wherein the breast cancer cell of the subject is characterised by according to following formula Weighting substrate and tube chamber A graders score be more than -0.3：

Wherein described substrate barycenter grader score and the tube chamber A barycenter grader score be for subject breast cancer it is thin Expression of intrinsic gene set of the born of the same parents shown in table 1 in the cell is determined.

39. the method according to claim 38, wherein the breast cancer cell of the subject is characterised by the base of weighting Bottom and tube chamber A graders score are more than -0.2.

40. the method according to claim 39, wherein the breast cancer cell of the subject is characterised by the base of weighting Bottom and tube chamber A graders score are more than -0.25.

41. the method according to claim 37, wherein the breast cancer cell of the subject is characterised by the institute from table 1 The substrate barycenter grader score that expression of the intrinsic gene set shown in the cell is determined is less than or equal to 0.9.

42. method according to claim 41, wherein the breast cancer cell of the subject is characterised by substrate barycenter Grader score is less than or equal to 0.6.

43. method according to claim 41, wherein the breast cancer cell of the subject is characterised by substrate barycenter Grader score is in the range of 0.2 to 0.8.

44. method according to claim 43, wherein the breast cancer cell of the subject is characterised by substrate barycenter Grader score is in the range of 0.4 to 0.7.

45. the method according to any one of claim 37 to 44, wherein the breast cancer of the subject is characterised by The presence of androgen receptor positive tumor cell.

46. the method according to any one of claim 37 to 45, wherein the androgen receptor inhibitor is selected from：Grace is miscellaneous Shandong amine, Bicalutamide, Flutamide, Nilutamide, ARN509, ketoconazole, abiraterone acetate, VN/124-1 (TOK-001), Orteronel (TAK-700), Finasteride, galeterone, CPA, andarine, with and combinations thereof.

47. according to the method for claim 46, wherein androgen receptor inhibitor is the miscellaneous Shandong amine of grace.

48. method according to claim 47, wherein the miscellaneous Shandong amine of the grace is oral daily once, dosage is 160mg.

49. method according to claim 48, wherein the miscellaneous Shandong amine of the grace is used as the single glue for including the miscellaneous Shandong amine of 160mg grace Capsule is applied.

50. method according to claim 48, wherein the miscellaneous Shandong amine of the grace is applied in the form of four capsules, each capsule Include the miscellaneous Shandong amine of 40mg grace.

51. the method according to any one of claim 37 to 50, wherein the breast cancer comprising androgen receptor inhibitor Treatment is not also other anticancers of androgen receptor inhibitor comprising one or more.

52. method according to claim 51, wherein not being that other anticancers of androgen receptor inhibitor are selected from ring phosphorus Acid amides, fluorouracil, 5 FU 5 fluorouracil, methotrexate (MTX), thiotepa, carboplatin, cis-platinum, taxane, taxol, what protein was combined Taxol, docetaxel, vinorelbine, TAM, Raloxifene, Toremifene, fulvestrant, gemcitabine, Yi Li is replaced Health, Ipsapirone, Temozolomide, TPT, vincristine, vinblastine, eribulin, mutamycin, capecitabine, card Train his shore, Anastrozole, Exemestane, Letrozole, Leuprorelin, abarelix, Bath woods, Goserelin, tumer it is pregnant Ketone, Risedronate, Pamidronate, ibandronate, Alendronate, ground promise monoclonal antibody, zoledronate, toltrazuril list It is anti-, Lapatinib or Avastin, with and combinations thereof.

53. method according to claim 52, wherein described is not that other anticancers of androgen receptor inhibitor are purple China fir alcohol.

54. the method according to claim 37, in addition to test the subject to determine whether the subject has The step of including not being the breast cancer of breast cancer cell of substrate sample hypotype.

55. the method according to any one of claim 38 to 40, in addition to test the subject with determine it is described by The step of substrate and tube chamber A grader scores of the weighting of the breast cancer cell of examination person.

56. the method according to any one of claim 41 to 44, in addition to test the subject with determine it is described by The step of substrate barycenter grader score of the breast cancer cell of examination person.

57. method according to claim 40, wherein the subject does not receive or received except androgen receptor One wheel prior treatment of anticancer outside inhibitor is to treat triple negative breast cancer.

58. the method for triple negative breast cancer is treated in the subject for needing to treat, including：

(a) biological sample from subject is provided；

(b) biological sample is determined to determine whether biological sample is classified as substrate sample hypotype or another hypotype；With

If (c) biological sample is classified as not be substrate sample hypotype, subject is applied and includes androgen receptor inhibitor Breast cancer treatment, so as to treat the breast cancer of subject.

59. method according to claim 58, wherein determining biological sample to determine whether biological sample is classified as base Original pattern hypotype or another hypotype are carried out by detecting the expression of the intrinsic gene shown in table 1.

60. method according to claim 59, including：

(a) substrate barycenter grader score and the classification of tube chamber A barycenter of sample are determined from the expression of the intrinsic gene set shown in table 1 Device score；With

(b) substrate of weighting is calculated from substrate barycenter grader score and tube chamber A barycenter graders score according to following equation With tube chamber A grader scores：

With

If the substrate and tube chamber A graders score of wherein described weighting are more than -0.3, breast cancer is applied to the subject Treatment.

61. method according to claim 60, if wherein the substrate and tube chamber A graders score of weighting are more than -0.2, Then apply breast cancer treatment.

62. method according to claim 61, if wherein the substrate and tube chamber A graders score of the weighting be more than- 0.25, then using breast cancer treatment.

63. method according to claim 59, includes the base for expressing determination sample of the intrinsic gene set shown in table 1 Substrate heart grader score, if wherein substrate barycenter grader score is less than or equal to 0.9, using breast cancer treatment.

64. method according to claim 63, if wherein substrate barycenter grader score is applied less than or equal to 0.6 Use breast cancer treatment.

65. method according to claim 63, if wherein substrate barycenter grader score is in the range of 0.2 to 0.8, Breast cancer treatment then is applied to subject.

66. method according to claim 65, if wherein substrate barycenter grader score is in the range of 0.4 to 0.7, Breast cancer treatment then is applied to subject.

67. the method according to any one of claim 58 to 66, wherein the breast cancer of the subject is characterised by The presence of androgen receptor positive tumor cell.

68. the method according to any one of claim 58 to 67, wherein the androgen receptor inhibitor is miscellaneous selected from grace Shandong amine, Bicalutamide, Flutamide, Nilutamide, ARN509, ketoconazole, abiraterone acetate, VN/124-1 (TOK-001), Orteronel (TAK-700), Finasteride, galeterone, CPA, andarine, with and combinations thereof.

69. method according to claim 68, wherein the androgen receptor inhibitor is the miscellaneous Shandong amine of grace.

70. method according to claim 69, wherein the miscellaneous Shandong amine of the grace is oral daily once, dosage is 160mg.

71. method according to claim 70, wherein the miscellaneous Shandong amine of the grace is used as the single glue for including the miscellaneous Shandong amine of 160mg grace Capsule is applied.

72. method according to claim 70, wherein the miscellaneous Shandong amine of the grace is applied in the form of four capsules, each capsule Include the miscellaneous Shandong amine of 40mg grace.

73. the method according to any one of claim 58 to 72, wherein the breast cancer comprising androgen receptor inhibitor Treatment is not also other anticancers of androgen receptor inhibitor comprising one or more.

74. the method according to claim 73, wherein described is not that other anticancers of androgen receptor inhibitor are selected from Endoxan, fluorouracil, 5 FU 5 fluorouracil, methotrexate (MTX), thiotepa, carboplatin, cis-platinum, taxane, taxol, protein knot The taxol of conjunction, docetaxel, vinorelbine, TAM, Raloxifene, Toremifene, fulvestrant, gemcitabine, she It is vertical to replace health, Ipsapirone, Temozolomide, TPT, vincristine, vinblastine, eribulin, mutamycin, Ka Peita Shore, capecitabine, Anastrozole, Exemestane, Letrozole, Leuprorelin, abarelix, Bath woods, Goserelin, tumer Ground progesterone, Risedronate, Pamidronate, ibandronate, Alendronate, ground promise monoclonal antibody, zoledronate, toltrazuril Monoclonal antibody, Lapatinib or Avastin, with and combinations thereof.

75. according to the method for claim 74, wherein described is not that other anticancers of androgen receptor inhibitor are taxols.

76. the method according to any one of claim 58 to 75, wherein the biological sample is selected from cell, tissue and body Liquid.

77. the method according to claim 76, wherein the biological sample includes breast tissue or cell.

78. the method described in claim 77, wherein the tissue is obtained from biopsy.

79. the method according to claim 77, wherein the body fluid is selected from blood, lymph, urine, saliva, from conduit The liquid and nipple aspirate of irrigating solution.

80. method according to claim 62, wherein the subject does not receive or received except androgen receptor One wheel prior treatment of anticancer outside inhibitor is to treat triple negative breast cancer.